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PubMed1999

Relative abundance of thrombospondin 2 and thrombospondin 3 mRNAs in human tissues.

The levels of thrombospondin 2 (TSP2) and thrombospondin 3 (TSP3) mRNAs in a variety of human tissues were determined by analysis of multiple-tissue mRNA dot blots. For TSP2 mRNA, aorta and fetal heart had the greatest relative abundance. High levels were also detected for muscle, fetal, endocrine, immune, and nerve tissues. The pattern of expression of TSP3 mRNA was very different: kidney, pituitary gland, trachea, uterus, and fetal kidney had the greatest abundance. In general, TSP3 mRNA was expressed at high levels in endocrine, muscle, and fetal tissues. In addition to the tissue-specific differences, a more even distribution of TSP3 mRNA among tissues was observed. The high relative abundance of the two mRNAs in a variety of tissues and the tissue-specific differences in expression could be significant for understanding the diverse roles implicated for TSP2 and TSP3.

Blotting, Northern↗
PubMed2004

Decreased expressions of thrombospondin 2 in cyclosporin A-induced gingival overgrowth.

OBJECTIVES: Cyclosporin A (CsA) is known to elicit fibrous gingival overgrowth with changes of blood vessel profiles. In this study, we examined the expression of several angiogenic and angiostatic genes during the development of CsA-induced gingival overgrowth. METHODS: For the development of gingival overgrowth, Sprague-Dawley rats received subcutaneous injections of CsA in daily doses of 5, 10, 15 mg/kg body weight for 6 weeks, and another group received 10 mg/kg of CsA for 3, 6, and 12 weeks. Human gingival tissues were obtained from three CsA-treated patients following the gingivectomy procedure and from three healthy patients following the crown-lengthening procedure as a control. Gingival fibroblasts were isolated from the healthy gingival tissues of the rat or the human, and cultured with 250-1000 ng/ml of CsA. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that expressions of some angiogenic genes such as angiopoietin 1, basic fibroblast growth factor, and vascular endothelial growth factor, and angiostatic genes such as angiopoietin 2, brain-specific angiogenesis inhibitor 1 and 2, and thrombospondin 1 were not changed significantly in both gingival tissues and cultured fibroblast cells under the CsA treatments. However, expression of thrombospondin 2 (TSP2) decreased dose- and time-dependently in rat and human gingival tissues. Western blot analyses showed that the expression of TSP2 protein was dose-dependently reduced by the CsA treatments in human cultured gingival fibroblasts. CONCLUSIONS: These results indicate that the decrease in angiostatic TSP2 expression may be attributed to the CsA-induced gingival vascularization rather than to the increased expression of angiogenic genes. It suggests that TSP2 is involved in the development of CsA-induced gingival overgrowth with the gingival vascularization.

Angiogenesis Inhibitors↗
PubMed2001

Disulfide connectivity of recombinant C-terminal region of human thrombospondin 2.

The thrombospondin (TSP) family of extracellular glycoproteins consists of five members in vertebrates, TSP1 to -4 and TSP5/cartilage oligomeric matrix protein, and a single member in Drosophila. TSPs are modular multimeric proteins. The C-terminal end of a monomer consists of 3-6 EGF-like modules; seven tandem 23-, 36-, or 38-residue aspartate-rich, Ca(2+)-binding repeats; and an approximately 230-residue C-terminal sequence. The Ca(2+)-binding repeats and C-terminal sequence are spaced almost exactly the same in different TSPs and share many blocks of identical residues. We studied the C-terminal portion of human TSP2 from the third EGF-like module through the end of the protein (E3CaG2). E3CaG2, CaG2 lacking the EGF module, and Ca2 composed of only the Ca(2+)-binding repeats were expressed using recombinant baculoviruses and purified from conditioned media of insect cells. As previously described for intact TSP1, E3CaG2 bound Ca(2+) in a cooperative manner as assessed by equilibrium dialysis, and its circular dichroism spectrum was sensitive to the presence of Ca(2+). Mass spectrometry of the recombinant proteins digested with endoproteinase Asp-N revealed that disulfide pairing of the 18 cysteines in the Ca(2+)-binding repeats and C-terminal sequence is sequential, i.e. a 1-2, 3-4, 5-6, etc., pattern.

Amino Acid Sequence↗
PubMed1999

Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene.

Mice that lack the extracellular matrix protein thrombospondin 2 have, among several abnormalities, an increase in vascular density, abnormal collagen fibrils, and dermal fibroblasts that are defective in adhesion. These findings suggested that responses involving these processes, such as wound healing, might be altered. To investigate the healing process, excisional wounds were made with the aid of a biopsy punch. Such wounds, observed over a 14 d period, appeared to heal at an accelerated rate and with less scarring in thrombospondin 2-null mice. Histologic analysis of thrombospondin 2-null wound sites revealed the presence of an irregularly organized and highly vascularized granulation tissue. In addition, thrombospondin 2-null wounds retained a higher total cellular content, than control wounds. No differences in wound re-epithelization rates were observed, but thrombospondin 2-null epithelia formed rete pegs and were thicker than control epithelia. By immunohistochemistry, we detected elevated levels and an irregular deposition pattern for fibronectin in thrombospondin 2-null wounds, observations that correlated with the abnormal collagen organization in the granulation tissue. Immunostaining for thrombospondin 2 in control wounds showed that the protein is present in both early and late wounds, in a scattered cell-associated pattern or widely distributed cell- and matrix-associated pattern, respectively. Our results suggest that thrombospondin 2 plays a crucial part in the organization and vascularization of the granulation tissue during healing, possibly by modulating fibroblast-matrix interactions in early wounds and regulating the extent of angiogenesis in late wounds.

Animals↗
PubMed2005

Thrombospondin 1, thrombospondin 2 and the eye.

Thrombospondin 1 and thrombospondin 2 (TSP1 and TSP2), which comprise the subgroup A thrombospondins, are matricellular proteins. As matricellular proteins, they modulate interactions between cells and the cellular environment, regulate cell adhesion and typically are expressed during tissue formative processes. In general, TSP1 and TSP2 counter angiogenesis (including tumour angiogenesis) and play important but contrasting roles during cutaneous repair. The two proteins are involved in development, including that of the eye, although evidence suggests that they have their greatest impact during tissue production in the adult. In the normal adult eye, they tend to be found at sites of ongoing matrix synthesis or cell-matrix interactions. At these sites, the two proteins possibly influence cellular differentiation and/or basement membrane deposition. TSP1 is also present in the intraocular fluids and drainage pathway, where it may function in maintaining the anti-angiogenic environment and in intraocular pressure control, respectively. TSP1 could also be involved in ocular immune privilege. Unlike in skin wounds, where TSP1 is derived from the blood and is present only in the early phases of repair, ocular tissue damage appears to lead to protacted TSP1 synthesis by local cells. This response might help suppress angiogenesis in the transparent tissues of the eye and so lessen visual axis opacification following injury. However, TSP2, which is also produced by damaged ophthalmic tissue and may be especially important in matrix organisation, seems to augment contraction in anomalous intraocular fibrosis. Elucidating the roles of TSP1 and TSP2 in ocular physiology and pathobiology may lead to improved therapies for neovascular, neoplastic, reparative and other ophthalmic diseases.

Animals↗
PubMed1993

The in situ localization of tenascin splice variants and thrombospondin 2 mRNA in the avian embryo.

Tenascin and thrombospondin belong to the growing family of extracellular matrix glycoproteins believed to have an anti-adhesive function during development. Immunohistochemistry has been used to identify these proteins in the developing central nervous system, in the matrix surrounding peripheral neurons, and in connective tissue. The antibodies used in most of these studies, however, could not distinguish between different splice variants (tenascin) nor different genetic forms (thrombospondin). For this reason, we used the reverse transcriptase polymerase chain reaction to generate DNA probes that are specific to the transcripts of high M(r) tenascin and thrombospondin 2. These probes were then used for an in situ hybridization study to determine the cellular origins of specific tenascin and thrombospondin forms throughout the development of the chick. The mRNA encoding high M(r) tenascin was found associated with motile cells and in tissues undergoing dynamic modeling: migrating glia, epithelial glia used as a substratum for migrating neurons, the growing tips of lung buds, and during osteogenesis. In contrast, the mRNAs of low M(r) tenascin were concentrated in areas of cartilage deposition and chondrocyte proliferation. Thrombospondin 2 mRNA was not detected in the developing central nervous system at any time during development by in situ hybridization. In contrast, it was found in embryonic mesenchyme, perichondrium, epimysium, and endothelial cells. Thrombospondin 2 mRNA was detected in poly(A) RNA isolated from embryonic spinal cord and cerebellum by polymerase chain reaction, though it was not detected in poly(A) RNA from the avascular retina. Thus, thrombospondin 2 mRNA may be present in the developing brain at low levels in endothelial cells or blood cells. These data support the notion that tenascin splice variants have distinct roles during development, and that thrombospondin 2 is more likely to be playing a role associated with the morphogenesis of connective tissue than neuronal development.

Animals↗
PubMed2000

Increased marrow-derived osteoprogenitor cells and endosteal bone formation in mice lacking thrombospondin 2.

The phenotype of thrombospondin 2 (TSP2)-null mice includes abnormalities in collagen fibrils and increases in ligamentous laxity, vascular density, and bleeding time. In this study, analyses by computerized tomography (CT) revealed that cortical density was increased in long bones of TSP2-null mice. Histomorphometric analysis showed that the mid-diaphyseal endosteal bone formation rate (BFR) of TSP2-null mice was increased in comparison with that of wild-type (WT) animals. Although microgeometric analysis showed that periosteal and endosteal radii were reduced, the mechanical properties of femurs from TSP2-null mice were not significantly different from those of controls, presumably because of the concomitant increase in endosteal bone mass. Bone loss in ovariectomized mice was equivalent for WT and mutant mice, a finding that indicates that TSP2-null animals are capable of normal bone resorption. To further explore the cellular basis for the increased endosteal BFR in TSP2-null mice, marrow stromal cells (MSCs) were isolated and examined in vitro. These cells were found to be present in increased numbers in a colony forming unit (CFU) assay and showed an increased rate of proliferation in vitro. We conclude that TSP2 regulates the proliferation of osteoblast progenitors, directly or indirectly, and that in its absence endosteal bone formation is increased.

Animals↗
PubMed1997

Analysis of the promoter and transcription start sites of the human thrombospondin 2 gene (THBS2).

To identify features of the human thrombospondin 2 gene (THBS2) important for regulation of expression, the sequences of 5 kb of the promoter/5' flank and 3 kb of transcribed and intronic DNA were determined. Two repetitive sequences were found: an MLT1c element located 2.2 kb 5' of exon 1 and, further 5', 1.8 kb of a Tigger1 element. Putative transcription factor binding sites that might be significant for THBS2 regulation included p53, NF-kappaB, Spl, Myc-CF1, NF-Y, CF1, AP1, and GATA sites. Alignment of the promoter/5' flank sequence with the mouse Thbs2 promoter revealed 78% identity for a 450 bp region immediately upstream from the mouse transcription start site. No significant homology was detected between the human thrombospondin 2 and thrombospondin 1 promoters. Comparison of the THBS2 genomic and cDNA sequences revealed that, in contrast to Thbs2, exon 1 is divided into exons 1A and 1B by a small (93 bp) intron. The transcription start site was investigated by a PCR procedure and by 5' RACE, and yielded a size for exon 1A of at least 186 bp. Tissue-specific differences in transcription start sites were found, with transcript lengths in the order: fetal lung > adult lung > fetal brain. These results suggest that tissue-specific differences in expression of the THBS2 gene may be determined, in part, by selection of the transcription start site and resulting differences in the 5' untranslated region.

Amino Acid Sequence↗
PubMed2000

Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis.

Thrombospondin 2 (TSP2)-null mice, generated by targeted disruption of the Thbs2 gene, display a complex phenotype that is characterized, in part, by a variety of connective tissue abnormalities and increased vascular density in skin and subcutaneous tissues. In this paper we summarize the evidence that TSP2 functions as a matricellular protein to influence cell function by modulating cell-matrix interactions, rather than acting as an integral component of the matrix. Thus, the structurally abnormal collagen fibrils detected in skin appear to be the consequence of the defective adhesion demonstrated by dermal fibroblasts in culture that, in turn, result from increased matrix metalloproteinase 2 (MMP2, gelatinase A) production by these cells. Corroborating evidence for such a mode of action comes from transmission electron microscopic images of developing flexor muscle tendons that show distinct abnormalities in fibroblast-collagen fibril interactions in TSP2-null tissue. The increased vascular density seen in skin of TSP2-null mice can be reproduced in a number of models of injury, including subcutaneous implantation of polyvinyl alcohol sponges and silicone rubber discs, and excisional skin wounds. Experiments are proposed to distinguish between a primarily endothelial cell versus an extracellular matrix origin for the increased angiogenesis in TSP2-null mice.

Animals↗
PubMed2000

Extracellular matrix metalloproteinase 2 levels are regulated by the low density lipoprotein-related scavenger receptor and thrombospondin 2.

We have recently shown that the adhesive defect observed in dermal fibroblasts derived from thrombospondin 2 (TSP2)-null mice results from an increase in matrix metalloproteinase 2 (MMP2) levels (Yang, Z., Kyriakides, T. R., and Bornstein, P. (2000) Mol. Biol. Cell 11, 3353-3364). Adhesion was restored by replacement of TSP2 and by inhibitors of MMP2 activity. In pursuing the observation that TSP2 and MMP2 interact, we now demonstrate that this interaction is required for optimal clearance of extracellular MMP2 by fibroblasts. Since TSP2 is known to be endocytosed by the scavenger receptor, low density lipoprotein receptor-related protein (LRP), we determined whether interference with LRP function affected fibroblast adhesion and/or extracellular MMP2 levels. Addition of heparin, which competes for the binding of TSP2 to LRP coreceptor proteoglycans, inhibited adhesion of control but not TSP2-null cells, and a blocking antibody to LRP as well as the LRP inhibitor, receptor-associated protein, also inhibited adhesion and increased MMP2 levels only in control fibroblasts. TSP2 did not inhibit active MMP2 directly and did not inhibit the activation of pro-MMP2. Finally, the internalization of 125I-MMP2 was reduced in TSP2-null compared with control fibroblasts. We propose that clearance of MMP2-TSP2 complexes by LRP is an important mechanism for the regulation of extracellular MMP2 levels in fibroblasts, and perhaps in other cells. Thus, some features of the phenotype of TSP2-null mice, such as abnormal collagen fibrillogenesis, accelerated wound healing, and increased angiogenesis, could result in part from increased MMP2 activity.

Animals↗
PubMed1999

Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity.

Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired.

Animals↗
PubMed2003

Keratocyte matrix interactions and thrombospondin 2.

PURPOSE: To determine whether human keratocytes synthesize thrombospondins 2 and 3 (TSP-2, TSP-3) in a collagen matrix and the effect of addition of antibodies to TSP-2 and TSP-3 on keratocyte-populated collagen matrix contraction. METHODS: Keratocyte-populated collagen matrices were evaluated for TSP-2 and TSP-3 mRNA. Sections of matrices were stained by immunohistochemistry for TSP-2 and TSP-3. Keratocyte populated collagen matrices were treated with antibodies specific for TSP-2 and TSP-3 and these preparations were evaluated for contraction and keratocyte morphology. RESULTS: Keratocyte derived fibroblasts in collagen matrices contained TSP-2 and TSP-3 mRNA, and the cells were immunoreactive for both proteins. Compared to controls, an antibody specific to the N-terminal domain of TSP-2 significantly inhibited matrix contraction for up to 10 days at a concentration of 20 microg/ml antibody. At 2 microg/ml TSP-2 antibody concentration significant inhibition occurred up to 3 days. Removal of the antibody from the media reversed the inhibitory effect. Cultured keratocytes in TSP-2 treated collagen matrices appeared more rounded than keratocytes in control matrices. An antibody specific to TSP-3 had no effect on matrix contraction or keratocyte morphology. CONCLUSIONS: Keratocyte derived fibroblasts synthesize TSP-2 and TSP-3 when seeded in collagen matrices. Antibody specific to TSP-2 reversibly inhibits matrix contraction. TSP-2 may play a key role in keratocyte/collagen matrix interactions, as may occur during corneal stromal repair.

Cell Adhesion Molecules↗
PubMed1999

Detection of exon skipping and retained introns in transcription of the human thrombospondin 2 gene.

Alternative transcripts of the gene for human thrombospondin 2 (TSP2), an extracellular glycoprotein, have been identified using a PCR procedure. Species that show exon skipping and/or retained introns were revealed. In particular, a species was characterized in which exon 3 has been spliced from the sequence. This transcript is otherwise intact from exon 1A to exon 22. Transcripts which retain intron 1A, intron 1B, or intron 2 were also identified. Tissue-specific differences were evident in the transcripts with retained introns. In addition, a species which both retained intron 1B and skipped exon 3 was revealed. The existence of these alternative transcripts of the human TSP2 gene could be important for understanding the diverse functions and tissue-specific expression implicated for TSP2.

Alternative Splicing↗
PubMed2003

Thrombospondin 2 regulates cell proliferation induced by Rac1 redox-dependent signaling.

Thrombospondin 2 (TSP2) is a matricellular protein controlling the apoptosis-proliferation balance in endothelial cells. Little is known about its transcriptional regulation compared with that of TSP1. We found that overexpression of a constitutively active mutant of Rac (Rac(V12)) specifically increases TSP2 mRNA levels without affecting TSP1 in human aortic endothelial cells (HAEC). Moreover, TSP2 induction by Rac(V12) is dependent upon reactive oxygen species (ROS) production, as gp91ds-tat peptide, an inhibitor of NADPH oxidase, and the flavoprotein inhibitor diphenylene iodinium (DPI) block TSP2 synthesis. Furthermore, we found that increasing Rac(V12) expression results in a biphasic proliferative curve, with proliferation initially increasing as Rac(V12) expression increases and then returning to levels less than that of control cells at higher expression. This growth inhibition is mediated by TSP2, as either DPI treatment, which blocks TSP2 synthesis, or pan-TSP blocking antibodies restore the proliferative ability of HAEC with high expression. Mechanistically, we show that the effect of TSP2 on cell proliferation is independent of the antiangiogenic TSP2 Hep1 sequence, which is capable of altering actin cytoskeletal reorganization but not proliferation in our experimental conditions. Finally, we show in vivo that Rac-induced TSP2 expression is observed in the aorta of transgenic mice selectively expressing Rac(V12) in smooth muscle cells. These results identify Rac-induced ROS as a new pathway involved in the regulation of TSP2 expression.

Actins↗
PubMed2000

Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2.

Thrombospondin 2 (TSP2)-null mice, generated by disruption of the Thbs2 gene, display a variety of connective tissue abnormalities, including fragile skin and the presence of abnormally large collagen fibrils with irregular contours in skin and tendon. In this study we demonstrate that TSP2-null skin fibroblasts show a defect in attachment to a number of matrix proteins, and a reduction in cell spreading. To investigate the molecular mechanisms responsible for these abnormal cell-matrix interactions, we compared the levels of matrix metalloproteinases (MMPs) in wild-type and mutant fibroblasts. Isolation and analysis of gelatinases from conditioned media by gelatin-agarose affinity chromatography and gelatinolytic assays demonstrated that TSP2-null fibroblasts produce a 2-fold increase in gelatinase A (MMP2) compared with wild-type cells. The adhesive defect was corrected by treatment of TSP2-null fibroblasts with soluble TSP2, with the MMP inhibitors BB94 and tissue inhibitor of metalloproteinase-2, and with a neutralizing antibody to MMP2. Moreover, stable transfection of TSP2-null fibroblasts with mouse TSP2 cDNA corrected both the adhesive defect and the altered expression of MMP2. Finally, MMP2 was shown to interact with TSP2 in a direct-binding plate assay. We conclude that TSP2 plays an important role in cell-matrix interactions, and that a deficiency in the protein results in increased levels of MMP2 that contribute to the adhesive defect in TSP2-null fibroblasts and could play a role in the complex phenotype of TSP2-null mice.

Animals↗
PubMed2004

Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis.

Thrombospondin 2 (TSP2), a matricellular protein with a primary role in modulating cell-matrix interactions, has been implicated in tissue repair and foreign body responses. Here we show that TSP2 has regulatory function in the chronic inflammatory lesions of rheumatoid arthritis. Tissue TSP2, produced by synovial fibroblasts, endothelial cells, and macrophages correlated not only with the intensity of angiogenesis but also with the architecture of lymphoid infiltrates. Synovial tissues with diffuse inflammatory infiltrates had high levels of TSP2, whereas synovial tissues with ectopic germinal center reactions and T cell-B cell aggregates produced low levels. Cell-based gene therapy with TSP2 was used to examine the in vivo effects of the matrix protein on neoangiogenesis and lymphoid organization. Human synovium-severe combined immunodeficiency (SCID) mouse chimeras were treated with TSP2-transfected fibroblasts deposited into the peritoneum. Overexpression of TSP2 led to the accumulation of TSP2 protein in the inflamed synovium and resulted in a prompt inhibition of lesional vascularization. Beside its anti-angiogenic activity, TSP2 also suppressed the production of the proinflammatory mediators, interferon-gamma and tumor necrosis factor-alpha, and induced the depletion of tissue-residing T cells. We propose that TSP2 is an endogenous regulator of angiogenesis and autoimmune inflammation in the synovium and represents a protective mechanism preventing ectopic lympho-organogenesis and persistent inflammation in this tissue site.

Animals↗
PubMed2002

Differential expression of thrombospondin 2 in primary and metastatic malignant melanoma.

In the present report we used oligonucleotide microarray analysis for the identification of genes characterizing the late-stage metastatic phenotype of malignant melanoma. A panel of 5,600 genes was analysed in a low aggressive and a highly aggressive (metastatic) human malignant melanoma cell line, respectively. More than 300 differentially regulated genes were identified. High metastatic potential correlated with upregulated mRNA expression in the groups of cytoskeletal proteins, apoptosis and cell cycle proteins, GTP binding proteins and oncogenes, extracellular ligands and receptors, transcription and translation factors. In contrast, most angiogenesis factors, extracellular matrix molecules, and melanoma-specific antigens were downregulated. Particular target genes were further analysed by in situ hybridization and immunohistochemical staining of primary malignant melanomas and melanoma metastases. Here, we show that thrombospondin 2, an extracellular matrix molecule which was differentially regulated in the microarray analysis, was strongly expressed in melanoma metastases, but not in primary tumours. The identification of thrombospondin 2 as a target molecule emphasizes the importance of cell-matrix interactions for the pathogenesis of malignant melanoma metastasis and may open future perspectives for treatment of this tumour.

Blotting, Northern↗
PubMed2002

Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells.

This study was performed to characterize human thrombospondin 2 (TSP2). TSP2 has recently attracted attention as an endogenous negative regulator of angiogenesis in tumorigenesis. We cloned and transfected human TSP2 cDNA into the human colon cancer cell line SW-480. Stable transfectants (TSP2-1, TSP2-6) overexpressing TSP2 were established. Growth characteristics of TSP2-transfectants were investigated in vitro and in vivo. TSP2-transfectants showed similar growth properties to vector-transfectants and wild-type SW-480 cells. The overexpression of transfected human TSP2 cDNA did not affect proliferation of SW-480 cells. When the conditioned media of TSP2-transfectants were added to cultures of bovine pulmonary microvascular endothelial cells (BPMEC), the BPMEC proliferation was significantly inhibited. These results suggested that human TSP2 is a potential inhibitor of angiogenesis.

Angiogenesis Inhibitors↗