Biomedical subjects

S L Schor

Publications and source records attributed to S L Schor.

At least 19 recordsLinked to original sources

PubMed2006

A novel 'sandwich' assay for quantifying chemo-regulated cell migration within 3-dimensional matrices: wound healing cytokines exhibit distinct motogenic activities compared to the transmembrane assay.

The extracellular matrix profoundly affects cellular response to soluble motogens. In view of this critical aspect of matrix functionality, we have developed a novel assay to quantify chemo-regulated cell migration within biologically relevant 3-dimensional matrices. In this "sandwich" assay, target cells are plated at the interface between an upper and lower matrix compartment, either in the presence of an isotropic (uniform) or anisotropic (gradient) spatial distribution of test motogen. Cell migration in response to the different conditions is ascertained by quantifying their subsequent disposition within the upper and lower matrix compartments. The objective of this study has been to compare the motogenic activities of platelet-derived growth factor (PDGF-AB) and transforming growth factor-beta isoforms (TGF-beta1, -beta2 and -beta3) in the sandwich assay and the commonly employed transmembrane assay. As previously reported, dermal fibroblasts exhibited a motogenic response to isotropic and anisotropic distributions of all tested cytokines in the transmembrane assay. In contrast, only PDGF-AB and TGF-beta3 were active in the sandwich assay, each eliciting directionally unbiased (symmetrical) migration into the upper and lower type I collagen matrices in response to an isotropic cytokine distribution and a directionally biased response to an anisotropic distribution. TGF-beta1 and -beta2 were completely devoid of motogenic activity. These results are consistent with the reported differential bioactivities of PDGF and TGF-beta3 compared to TGF-beta1 and -beta2 in animal models of wound healing and suggest that the sandwich assay provides a means of obtaining physiologically relevant data regarding chemo-regulated cell migration.

Animals↗

PubMed2006

Extraction of RNA from archival tissues and measurement of thrombospondin-1 mRNA in normal, dysplastic, and malignant oral tissues.

Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein implicated in the regulation of angiogenesis and tumour development. Our objectives were to ascertain the quantity and quality of RNA extracted from archival, formalin-fixed, paraffin embedded, oral tissues and their application in measuring the concentrations of TSP-1 mRNA in these tissues. We compared three techniques of isolation of RNA as well as related experimental variables. TSP-1 mRNA was measured in specimens of normal, dysplastic, and malignant oral tissues by real-time reverse transcriptase polymerase chain reaction (RT-PCR). RNA suitable for analysis by real-time RT-PCR was obtained by the three techniques tested, although the yield varied depending on the protocol used (range 0.2-3.6 microg/mm(3)). The mean (S.D.) concentrations of TSP-1 mRNA relative to 18S were 21.1 (7.2) in normal oral tissues (n=9), 11.0 (8.2) in dysplastic tissue (n=8) and 7.3 (5.3) in carcinomatous tissue (n=17). The difference between normal and carcinomatous specimens was significant (p=0.01). This reduction in expression of TSP-1 mRNA from normal to dysplasia to carcinoma may favour the angiogenic drive that accompanies the development of oral tumours.

Carcinoma, Squamous Cell↗

PubMed2003

Growth factors in the treatment of diabetic foot ulcers.

BACKGROUND: Chronic foot ulceration is a major source of morbidity in diabetic patients. Despite traditional comprehensive wound management, including vascular reconstruction, there remains a cohort of patients with non-responding wounds, often resulting in amputation. These wounds may benefit from molecular manipulation of growth factors to enhance the microcirculation. METHODS: A review of the current literature was performed using Pubmed, with secondary references obtained from key articles. RESULTS AND CONCLUSION: There has been a generally disappointing clinical outcome from growth factor trials, although topical platelet-derived growth factor has shown significant benefit and should be considered in non-healing, well perfused ulcers after failure of conventional wound care. The modulatory role of the extracellular matrix in the cellular response to growth factors and data from regenerative-type fetal wound healing are further areas of interest. The chemical induction of microvessel formation may become a future therapeutic option.

Diabetic Foot↗

PubMed2002

Microengineering as a tool to study substratum modulation and cell behaviour.

This research is an investigation of the means by which geometrical parameters (e.g. area and shape) and various surface attributes (materials and surface finish) of microengineered structures can modulate cellular response. This is based on biological observations indicating that: (i) the response of tissue cells to injury is determined by the net signal transduction response elicited by soluble regulatory molecules (e.g. cytokines), (ii) common matrix constituents (e.g. collagen) directly affect cell behaviour by the same signal transduction mechanisms mediating cytokine bioactivity, (iii) cellular response to cytokines is modulated by the precise nature of the extracellular matrix to which the target cells are adherent, including its biochemical composition and physical structure.

Biocompatible Materials↗

PubMed2001

Phenotypic and genetic alterations in mammary stroma: implications for tumour progression.

In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in the present review extend the repertoire of matrix signalling mechanisms, (1) introducing the concept of 'matrikines', these defined as proteinase-generated fragments of matrix macromolecules that display cryptic bioactivities not manifested by the native, full-length form of the molecule, and (2) indicating that a previously identified motogenic factor (migration stimulating factor [MSF]) produced by foetal and cancer patient fibroblasts is a genetically generated truncated isoform of fibronectin, which displays bioactivities cryptic in all previously identified fibronectin isoforms. These observations are discussed in the context of the contribution of a 'foetal-like' stroma to the progression of breast cancer.

Breast↗

PubMed2001

Expression of vascular endothelial growth factor in normal and tumour oral tissues assessed with different antibodies.

Expression of vascular endothelial growth factor (VEGF) in oral tissues was assessed using different antibodies. Quantitative and topographical differences were observed between paraffin and cryostat sections. Two polyclonal antibodies (PC36, PC37) differing in their cross-reactivity with VEGF121 (not recognized by PC36), were used to stain serial cryostat sections of normal oral mucosa (n = 8) and squamous cell carcinoma (n = 7). The expression of VEGF in the epithelium was overall higher with PC37 than with PC36, the difference being significant in normal oral mucosa (p = 0.001) but not in squamous cell carcinoma samples (p = 0.094). With PC36, VEGF expression was significantly higher in squamous cell carcinoma than in normal oral mucosa specimens, whereas the opposite was true with PC37. Our results suggest that the relative levels of isoform 121 to that of 165 (and possibly others) may be different in the tissues examined, with VEGF121 preferentially expressed in normal oral mucosa. Previously published conflicting results may, therefore, be due to the presence of variable ratios of VEGF isoforms in the tissues examined, combined with differences in the cross-reactivity of the antibodies used. VEGF isoforms 121, 165 and (for the first time) 189 were detected in two frozen oral tissues by polymerase chain reaction amplification. Quantification of specific VEGF isoforms will be required in future studies concerned with the clinical value of VEGF expression.

Antibodies↗

PubMed2001

Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisation.

The aim of this study was to assess whether vascular endothelial growth factor (VEGF) expression in oral tissues is associated with angiogenesis, disease progression or field cancerisation. Vascularity and VEGF immunoreactivity were quantified in 68 archival specimens including normal oral mucosa (NOM), dysplasia (DYS) and squamous cell carcinoma (SCC). Vascularity increased significantly with disease progression; it was also higher in NOM adjacent to SCC than in NOM from healthy tissue, suggesting an association with field cancerisation. VEGF expression in epithelial cells was evaluated using two antibodies and three indices. VEGF indices and vascularity were not directly correlated. The expression of VEGF was similar in all DYS and NOM specimens, whether or not adjacent to a concurrent lesion. A comparison of SCC with NOM or DYS led to opposite results, depending on the VEGF antibody and index used. We conclude that VEGF expression in the oral mucosa may play a physiological role, but does not appear to be associated with angiogenesis, field cancerisation or transition to dysplasia. Further studies concerned with tumour development require examining specific VEGF isoforms and standardisation of the methodology.

Antibodies↗

PubMed2000

Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to tumour progression.

Experimental animal models have demonstrated that angiogenesis is essential for tumour progression, whilst sustained tumour growth requires a positive balance between tumour cell proliferation and cell death (apoptosis). The aim of this study was to determine the relative contribution of apoptosis, proliferation, and angiogenesis to disease progression in the oral mucosa. Histological sections of 47 archival specimens were examined; these included four groups of oral tissues: normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and squamous cell carcinoma (n=18). Apoptotic cells were visualized by in-situ end-labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood vessels with von Willebrand factor (vWF) antibody. One-way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) increased significantly with disease progression from normal oral mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase from normal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was significant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and increases in both epithelial proliferation and apoptosis. Net epithelial growth results from proliferation starting earlier and proceeding at a higher rate than apoptosis.

Adolescent↗

PubMed1999

Motogenic and biosynthetic response of adult skin fibroblasts to TGF-beta isoforms (-1, -2 and -3) determined by 'tissue response unit': role of cell density and substratum.

We have recently demonstrated that the three principal mammalian isoforms of transforming growth factor beta (TGF-beta) exert distinct effects upon: (1) the migration of confluent adult fibroblasts into 3D gels of native type I collagen fibres (i.e. TGF-beta-1 and -2 had no apparent motogenic activity, whilst TGF-beta-3 induced a dose-dependent stimulation of cell migration); and (2) the synthesis of hyaluronan (HA) by these cells is also affected by the TGF-beta isoforms in a manner which parallels their effect on cell migration. The objective of the present study is to elucidate the manner in which this differential activity of the TGF-beta-1, -2 and -3 may be modulated by experimental parameters. Data presented in this communication indicate that cytokine bioactivity is determined by a combination of cell density and the nature of the macromolecular substratum. Thus, we now report that all three TGF-beta isoforms inhibit the migration of subconfluent cells in the collagen gel assay. Our data confirm that the migration of confluent cells is stimulated by TGF-beta-3 and further indicate that this motogenic activity is completely abrogated by either TGF-beta-1 or -2 when these are co-incubated with TGF-beta-3. In contrast to these results obtained using a native type I collagen substratum, all three isoforms stimulated adult fibroblast migration in the transmembrane assay (in which cells are adherent to a 2-D porous polycarbonate substratum). The precise effect of TGF-beta isoforms on HA synthesis was also affected by cell density and the nature of the substratum in a manner which paralleled their diverse effects on cell migration (i.e. stimulation, inhibition or no effect). Streptomyces hyaluronidase completely neutralized the TGF-beta-3-induced stimulation of confluent fibroblast migration, thus suggesting a mechanistic link between the cytokine-induced cell migration and HA synthesis under these conditions. Taken together, these data indicate that: (1) the bioactivity of TGF-beta-1, -2 and -3 are determined by cell density, the macromolecular substratum and the presence of other cytokines; and (2) it is therefore necessary to define cytokine bioactivity within the context of a larger 'tissue response unit' which more fully defines the activity state of the target cell and its microenvironment.

Adult↗

PubMed1999

The association between epithelial proliferation and disease progression in the oral mucosa.

The purpose of this study was to examine the possible association between epithelial proliferation and disease progression in the oral mucosa. Archival specimens of normal oral mucosa (n = 12), dysplasia (n = 17) and squamous cell carcinoma (n = 18) were sectioned and proliferating cells visualised by staining with Ki-67 antibody. The proliferative index of the epithelium (PI) was determined by total cell counts and point counting. Similar results were obtained using either method. Comparison of the three groups of tissues by one-way analysis of variance showed a significant increase in PI with increasing lesion severity (p < 0.001). The PI of both dysplasia and carcinoma groups was significantly higher than that of normal oral mucosa (p < 0.001). However, the difference between dysplasia and carcinoma groups was not significant. PI was not associated with tobacco or alcohol consumption. We therefore conclude that Ki-67 expression is an early marker of disease progression in the oral mucosa but, on its own, is not a good indicator of neoplastic transformation.

Adult↗

PubMed1999

Motogenic activity of IGD-containing synthetic peptides.

Although the IGD amino acid motif (iso-gly-asp) is a highly conserved feature of the fibronectin type I module, no biological activity has as yet been ascribed to it. We have previously reported that the gelatin-binding domain of fibronectin stimulates the migration of human skin fibroblasts into native, but not denatured, type I collagen substrata. Two IGD-containing type I modules are present within the gelatin-binding domain. The object of this study was to ascertain whether soluble synthetic peptides containing the IGD motif stimulate fibroblast migration. We found that IGD peptides stimulated fibroblast migration in the following order of activity: IGDS (as present in the ninth type I module) > IGDQ (as present in the seventh type I module) > IGD. The scrambled SDGI peptide and the well-characterised RGDS peptide were devoid of motogenic activity. The migratory response of fibroblasts to IGD-containing peptides consisted of two distinct phases: an initial period of peptide-mediated cell activation and a subsequent period of enhanced migration manifest in the absence of further IGD peptide. Cell activation was substratum-independent (occurring equally well on both native and denatured type I collagen substrata), whilst the manifestation of enhanced migration was persistent and substratum-dependent (being evident only by cells adherent to a native collagen substratum). Our data further indicated that cell activation (1) is elicited by a signal transduction cascade occurring within minutes of cell exposure to IGD-containing peptides, (2) is dependent upon integrin alphavbeta3 functionality, (3) involves the tyrosine phosphorylation of focal adhesion kinase (ppFAK125) and (4) is inhibited by signalling mediated through integrin alpha5beta1. The expression of migration stimulating activity by soluble IGD-containing peptides clearly distinguishes them from their RGD counterparts. This is the first identified biological activity of the highly conserved IGD motif and provides a rational platform for the development of a novel family of therapeutic compounds designed to stimulate cell migration in relevant clinical situations, such as impaired wound healing.

Amino Acid Motifs↗

PubMed1998

Differential motogenic and biosynthetic response of fetal and adult skin fibroblasts to TGF-beta isoforms.

Data are presented in this communication comparing fetal and adult fibroblasts with respect to the effects of transforming growth factor beta (TGF-beta) isoforms (-beta 1, -beta 2 and -beta 3) on cell migration and hyaluronan (HA) synthesis. Cell migration was assessed on three-dimensional native type I collagen substrata. Fetal and adult cells differed in terms of their motogenic response to the three TGF-beta isoforms in a manner which was modulated by cell density, i.e.: (1) the migration of subconfluent fetal cells was unaffected by TGF-beta 1 and -beta 2, but inhibited by TGF-beta 3, whilst the migration of subconfluent adult cells was inhibited by all three isoforms, and (2) the migration of confluent fetal cells was inhibited by all three TGF-beta isoforms, whilst the migration of confluent adult cells was unaffected by TGF-beta 1 and -beta 2, but stimulated by TGF-beta 3. This diverse pattern of motogenic response to the three TGF-beta isoforms was paralleled by similar effects on HA synthesis (i.e. inhibition, no effect or stimulation). Linear regression analysis revealed a significant correlation between cell migration and total HA synthesis (r2 = 0.861; P < 0.0001). Gel filtration chromatography of cell-produced HA indicated that the effects of TGF-beta isoforms on total HA synthesis reflected alterations in the relative production of high molecular mass species (M(r) > 10(6)). Taken together with previously published data, these observations indicate that (1) fetal and adult fibroblasts exhibit distinct responses to the three TGF-beta isoforms with respect to both cell migration and HA synthesis, (2) cellular response to the TGF-beta isoforms is modulated by cell density, and (3) TGF-beta 3 is the only isoform which stimulated cell migration and HA synthesis (with confluent adult cells).

Adult↗

PubMed1998

Regulation of fibroblast-induced collagen gel contraction by interleukin-1beta.

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo. In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1beta (IL-1beta) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1beta induced a statistically significant inhibition of gel contraction in all fibroblast cell types (P<0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.

Adult↗

PubMed1997

The association between tumour progression and vascularity in the oral mucosa.

Tumourigenesis in experimental models is associated with the formation of new blood vessels (angiogenesis). Recent studies have suggested that tumour angiogenic activity may be inferred in histological sections by measuring the density of the vasculature. The purpose of this study was to determine whether the transition from normal to dysplastic and neoplastic tissue in the oral mucosa is accompanied by quantitative or qualitative changes in the vascularity of the tissue, and how the estimate of vascularity is influenced by the vessel marker and method of assessment. A total of 100 specimens of normal oral mucosa, dysplastic lesions, and squamous cell carcinomas were examined. Sections were immunostained with the pan-endothelial antibodies to von Willebrand Factor (vWF) and CD31, or with an antibody to the alpha v beta 3 integrin, previously reported to be a marker of angiogenic vessels. Vascularity was quantitated by two different methods: highest microvascular density (h-MVD) and microvascular volume, as determined by point counting (MVV). The results showed that vascularity, measured by the MVV method using antibodies to either vWF or CD31, increased significantly (P < 0.0001) with disease progression from normal oral mucosa, through mild, moderate, and severe dysplasia to early and late carcinoma (76 paraffin-embedded tissues examined). In contrast, h-MVD did not discriminate between dysplastic lesions and carcinoma. A similar percentage of the total vessel volume (MVV) and density (h-MVD) were positive for alpha v beta 3 in 24 frozen tissues examined, including normal oral mucosa. It is concluded that there is a close association between vascularity and tumour progression in the oral mucosa. Morphometric analysis reflecting microvascular volume is more informative than the currently popular analysis of microvascular density. The expression of alpha v beta 3 in the vasculature of oral tissues does not necessarily reflect the presence of angiogenic vessels.

Carcinoma, Squamous Cell↗

PubMed1997

Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis.

Previous studies have indicated that fetal skin fibroblasts display an elevated level of migratory activity compared to adult cells and that this may result from inherent differences in the production of hyaluronan (HA) by these cells. Data presented in this communication indicate that the elevated level of fetal fibroblast migration into 3D-collagen gels and HA synthesis by these cells were not affected by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF). In contrast, both cell migration and HA synthesis by fetal fibroblasts were inhibited by transforming growth factor-betal (TGF-beta1). Adult fibroblasts responded to these cytokines in a distinct fashion: i.e. cell migration and HA synthesis were stimulated by EGF, PDGF, aFGF and bFGF, but remained unaffected by TGF-beta1. Gel-filtration chromatography revealed that these effects of cytokines on HA synthesis were predominantly confined to the production of high molecular mass (>106 kDa) species. Co-exposure of cells to both cytokines and Streptomyces hyaluronidase revealed that (1) the elevated migration of control fetal fibroblasts was inhibited by hyaluronidase, (2) this inhibition was partially restored by co-exposure to EGF, PDGF, aFGF and bFGF, but remained unaffected by TGF-beta1, (3) the migration of control adult fibroblasts was unaffected by hyaluronidase and partially stimulated by EGF, aFGF and bFGF (when compared to the effects of these cytokines on cells cultured in the absence of hyaluronidase) and (4) neither PDGF nor TGF-beta1 affected the migration of hyaluronidase-treated adult cells. Linear regression analysis revealed a significant correlation between cell migration and HA synthesis by both fetal and adult fibroblasts in the presence and absence of cytokines (r2=0.9277, P<0.0001), with the exception of adult fibroblasts exposed to PDGF. Taken together, these findings suggest that (1) the migration of fetal and adult fibroblasts is differentially modulated by exogenous cytokines and (2) with the possible exception of the effects of PDGF on adult fibroblasts, cytokine-induced modulation of cell migration appears to utilise both HA-dependent and HA-independent pathways.

Adult↗

PubMed1996

Differential effects of TGF-beta1 on hyaluronan synthesis by fetal and adult skin fibroblasts: implications for cell migration and wound healing.

Fetal wound healing differs from its adult counterpart in that it is regenerative and occurs without scarring. The matrix macromolecule hyaluronan (HA) and various cytokines, including members of the TGF-beta family, have been implicated in the control of scarring. We have previously reported that adult and fetal fibroblasts differ with respect to the effect of cell density on HA synthesis when cultured on plastic tissue culture dishes. Data regarding the effects of substratum and TGF-beta1 on HA synthesis by these cells are presented in this communication. Our results indicate that HA synthesis by both fetal and adult fibroblasts is (a) up-regulated by culture on a collagen substratum and (b) differentially regulated by TGF-beta1 in a manner which is dependent upon both substratum and cell density. TGF-beta1 stimulated HA synthesis by confluent fetal fibroblasts growing on a plastic substratum, but inhibited HA synthesis on a collagen substratum; these data underscore the important role of the substratum in determining the precise effect of TGF-beta1 on cell behavior. Related studies indicated that the migration of fetal and adult fibroblasts into the collagen substrata was modulated by TGF-beta1 in a manner identical to its effect on HA synthesis. These observations are discussed in terms of the contribution of distinct fibroblast subpopulations to wound healing and the manner in which this is regulated by matrix and cytokines.

Adult↗

PubMed1996

Subpopulations of fetal-like gingival fibroblasts: characterisation and potential significance for wound healing and the progression of periodontal disease.

Wound healing in the adult is commonly compromised by excessive scar formation. In contrast, fetal wound healing is a regenerative process characterised by the conspicuous absence of scarring. Available evidence suggests that phenotypic differences between fetal and adult fibroblasts are important determinants of these distinct modes of tissue repair. In this context, a number of groups (including our own) have documented differences between fetal and adult fibroblasts with respect to such potentially relevant characteristics as migratory activity, motogenic response to cytokines and the synthesis of motility factors, cytokines and matrix macromolecules. The oral mucosa appears to be a privileged site in the adult in that it continues to display a fetal-like mode of wound healing. Data are presented in this review indicating that a subpopulation of gingival fibroblasts expresses several 'fetal-like' phenotypic characteristics. These observations are discussed in terms of both the continued expression of a fetal-like mode of wound healing in the oral mucosa and the possible differential involvement of distinct fibroblast subpopulations in the progression of periodontal disease.

Adult↗

PubMed1996

Substratum-dependent stimulation of fibroblast migration by the gelatin-binding domain of fibronectin.

Nanomolar concentrations of native fibronectin and its RGDS-containing cell-binding domain have previously been reported to stimulate fibroblast migration in the transmembrane (or 'Boyden chamber') assay; in contrast, the gelatin-binding domain (GBD) of fibronectin has consistently been reported to be devoid of migration-stimulating activity in this assay. We have examined the effects of fibronectin and several of its purified functional domains on the migration of human skin fibroblasts in what is presumably a more physiologically relevant assay involving the movement of cells into a 3-D matrix of native type I collagen fibrils. We report that: (a) femtomolar concentrations of GBD stimulate fibroblast migration into such collagen matrices; and (b) fibronectin, as well as peptides containing all other of its functional domains, do not exhibit migration-stimulating activity when tested in the femtomolar to nanomolar concentration range (i.e. 0.1 pg/ml to 1 microgram/ml). The correct assignment of migration-stimulating activity to GBD, rather than to a contaminant, was confirmed by: (a) the use of several fibronectin and GBD purification protocols; (b) the neutralization of GBD migration-stimulating activity by monoclonal antibodies directed against epitopes present in this domain; (c) the time-dependent generation of migration-stimulating activity by the proteolytic degradation of native fibronectin; and (d) obtaining an identical dose-response curve with a genetically engineered GBD peptide. The cryptic migration-stimulating activity of GBD was not affected by the presence of serum or native fibronectin, but was inhibited by TGF-beta 1. Parallel experiments using the transmembrane assay confirmed that GBD was devoid of migration-stimulating activity in this assay when membranes coated with gelatin were used, but revealed that significant stimulation of migration was achieved with membranes coated with native type I collagen. Cells preincubated with GBD for 24 hours whilst growing on plastic tissue culture dishes and then plated onto native collagen matrices in the absence of further GBD also displayed an elevated migration compared to controls. Taken together, these observations suggest that: (a) the interaction of GBD with a putative cell surface receptor (and not the collagen substratum) initiates a persistent alteration in cell phenotype which is manifest by an increase in migratory activity when these cells are cultured on a native collagen substratum; and (b) GBD may play a hitherto unrecognised role in the control of cell migration in response to the local release of proteases during pathological processes, such as tumour invasion and wound repair.

Cell Movement↗