Biomedical subjects

I Saiki

Publications and source records attributed to I Saiki.

At least 127 records · Page 7Linked to original sources

PubMed1993

Anti-viral activity of sulfated chitin derivatives against Friend murine leukaemia and herpes simplex type-1 viruses.

Sulfated chitin derivatives, selected for their low toxicity and high inhibitory activity of melanoma metastasis, were examined for anti-viral activity against Friend murine leukaemia, herpes simplex type-1 (HSV) and Sendai viruses. Carboxymethyl chitin with a 7.66% degree of sulfation (SCM-chitin III) showed a significant inhibition of Friend murine leukaemia helper virus (F-MuLV) and HSV, but not of Sendai virus growth in vitro. Sulfated N-deacetylated chitin had a significant but weak activity against F-MuLV and HSV infections. Carboxymethyl chitin showed no effect on these infections in vitro. SCM-chitin III also exhibited anti-viral activity in vivo by suppressing the splenomegaly which was caused by prior infection of mice with FV, a complex of F-MuLV and spleen focus-forming virus.

Animals↗

PubMed1993

In vitro invasive potential and type IV collagenolytic activity of human renal cell carcinoma cells derived from primary and metastatic lesions.

We investigated in vitro invasiveness and type IV collagenolytic activity of cells from a primary and a metastatic lesion of a patient with renal cell carcinoma. The temporarily cultured cells (SRCC-1P) derived from the primary lesion and those (SRCC-1M) from the metastatic lesion exhibited positive staining for both cytokeratin and vimentin, indicating that they were of renal cell carcinoma origin. An in vitro invasion assay revealed that the cells of SRCC-1M were significantly more invasive than those of SRCC-1P, which showed only marginal invasion. Type IV collagenolytic activity correlated with the in vitro invasiveness, in which SRCC-1M apparently had the higher activity. These results indicate that type IV collagenolytic activity contributes to the invasiveness of the cells in vitro.

Adrenal Gland Neoplasms↗

PubMed1993

Antimetastatic activity of polymeric RGDT peptides conjugated with poly(ethylene glycol).

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n = 2 to 4), at a dose of 500 micrograms exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and anti-metastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis ("anti adhesion therapy").

Amino Acid Sequence↗

PubMed1993

Functional analysis of mononuclear cells infiltrating into tumors: establishment of T cell hybridomas exhibiting distinct interacting abilities with endothelial cells and extracellular matrix components.

We have established eleven T cell hybridoma cell lines to investigate mechanisms controlling interaction of T lymphocytes with endothelial cells as well as extracellular matrix (ECM) proteins at the clonal level. T cell hybridomas were characterized and subdivided into four groups on the basis of their interaction behavior with high endothelial venules (HEV). Group 1 (G1) exhibited strong adhesiveness. The binding was temperature- and divalent cation-dependent. Group 2 exhibited both adhesiveness and transendothelial migration (TEM, i.e., transmigration beneath the cytoplasm of endothelial cells). Group 3 exhibited strong TEM. G2 and G3 hybridomas exhibited temperature-independent and divalent cation-independent binding to HEV. Group 4 exhibited nonspecific adhesiveness to the surface of a slide glass. BW 5147, a parent of T cell hybridomas, was classified as G4. TEM was dependent on both the nature of T cell hybridomas and endothelial cells. TEM was completely temperature-dependent. TEM of G3 hybridomas was not divalent cation-dependent. Each group of T cell hybridomas interacted with various ECM components.

Amino Acid Sequence↗

PubMed1993

Antimetastatic effect by anti-adhesion therapy with cell-adhesive peptide of fibronectin in combination with anticancer drugs.

We have investigated the therapeutic effect of CH-271 fusion polypeptide containing both cell-binding domain (C-274) and heparin-binding domain (H-271) of fibronectin in combination with anticancer drugs such as doxorubicin (DOX) or mitomycin C (MMC) on tumor metastasis of different types of tumors. CH-271 fusion polypeptide alone significantly inhibited both liver and lung metastasis when it was co-injected with L5178Y-ML25 T-lymphoma, RAW117-H10 B-lymphoma or B16-BL6 melanoma cells, and spontaneous lung metastasis of B16-BL6 melanoma cells when administered i.v. seven times before or after surgical excision of the primary tumors. Combined treatments with CH-271 and either DOX or MMC significantly inhibited liver and lung metastasis of lymphoma or melanoma cells respectively, as compared with either treatment alone or the untreated control. Administrations of CH-271 and DOX in combination substantially prolonged the survival time of mice injected i.v. with L5178Y-ML25 cells. CH-271 or DOX was effective for inhibiting the invasion of L5178Y-ML25 cells into Matrigel in a concentration-dependent manner. Our previous study has shown that CH-271-mediated inhibition of tumor invasion may be due in part to the anti-cell adhesive property without affecting the cell growth, whereas the anti-invasive effect of DOX was established to have resulted from the growth inhibition of tumor cells. Moreover, the combination of CH-271 with DOX provided a more effective inhibition of tumor invasion into Matrigel than did either alone. Thus, we have demonstrated that the combination of anti-cell adhesive CH-271 and anticancer drugs such as DOX or MMC, i.e. anti-adhesion therapy and chemotherapy, is a new approach that offers enhanced (additive) inhibitory effects on tumor metastasis and invasion.

Amino Acid Sequence↗

PubMed1993

Synthetic Arg-Gly-Asp-Ser analogues of the cell recognition site of fibronectin that retain antimetastatic and anti-cell adhesive properties.

Synthetic peptide analogues of the Arg-Gly-Asp-Ser (RGDS) sequence of fibronectin in which the amino acid of Gly was substituted with another one, named X, i.e. Arg-X-Asp-Ser (R-X-DS), and N-terminal modified R-X-DS have been synthesized to examine their antimetastatic effects in murine lung or liver metastasis models, as well as the inhibitory effect on tumor cell invasion, migration and adhesion in vitro. R-X-DS [X = Leu (L) or D-Leu (1)], as well as RGDS at a high dose of 3000 micrograms, significantly reduced the number of lung tumor colonies when they were co-injected with B16-BL6 melanoma. At a dose of 1000 micrograms/mouse, N-terminal modified R-X-DS, i.e. acetyl-D-R-X-DS [AcDR-X-DS: X = G, L or I], showed a more potent inhibitory effect on the lung or liver metastasis of B16-BL6 melanoma or L5178Y-ML25 lymphoma cells, respectively, as compared with RGDS or R-X-DS. AcDRLDS and AcDRIDS prevented the invasion of B16-BL6 cells into Matrigel/fibronectin- and Matrigel/laminin- coated filters, haptotactic migration, and the adhesion of the cells to both fibronectin- and laminin-coated substrates, whereas AcDRGDS inhibited only fibronectin-mediated cell functions. The intermittent i.v. administration of a water soluble vinylpolymer [poly(carboxyethylmethacrylamide), poly(CEMA)] containing R-X-DS (X = L or 1) or RGDS, following the subcutaneous inoculation of B16-BL6 cells, significantly inhibited spontaneous Jung metastasis as compared with multiple administrations of RGDS, R-X-DS or the untreated control.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

[Inhibition of tumor cell adhesion and metastasis].

Since the establishment of an experimental metastasis model using some tumor metastatic cell lines, progress has been made in basic studies on tumor metastasis. In addition, the complex mechanisms of tumor metastasis have been elucidated by the cellular and molecular studies. Here we focus our attention on the relationship between tumor metastasis and cellular adhesiveness, a factor which is a critical determinant in tumor progression and metastasis. The roles of cell adhesive molecules in the metastatic process are also described. This type of study is invaluable in understanding the molecular and regulatory mechanisms of tumor metastasis. We also report the antimetastatic effect of some polypeptides of fibronectin in the extracellular matrices, poly (RGD) and recombinant fusion peptide containing cell- and heparin-binding domain of fibronectin (CH-271) in regulating the mechanism of tumor cell adhesion.

Animals↗

PubMed1992

Inhibition of tumor-induced angiogenesis by the administration of recombinant interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60).

The effect of the administration of recombinant interferon-gamma (rIFN-gamma) and a synthetic lipid A subunit analog (GLA-60) on angiogenesis induced by B16-BL6 melanoma was examined in syngeneic C57BL/6 mice. Intravenous administration of rIFN-gamma followed by GLA-60 (referred to as rIFN-gamma/GLA-60) induced endogenous production of tumor necrosis factor (TNF). This treatment on day 3 after tumor inoculation caused a marked decrease in the number of vessels oriented towards the tumor mass (angiogenic response) and tumor size over a period of 9 days. In contrast, neither rIFN-gamma nor GLA-60 alone, nor GLA-60/rIFN-gamma (reverse sequence of administration), which is unable to induce the production of TNF in the serum, had any effect. Sera induced by the treatment with rIFN-gamma/GLA-60, and recombinant TNF, inhibited the in vitro growth of lung endothelial cells which is considered to be one of the essential events in tumor neovascularization. Multiple i.v. treatments with rIFN-gamma/GLA-60 on days 5, 8 and 11 after s.c. implantation of tumor significantly inhibited primary tumor growth by the amputation time (day 20) and lung metastasis of B16-BL6 cells on day 34, while other treatment modalities had no such effect. Our results indicate that inhibition of lung-tumor metastasis by rIFN-gamma/GLA-60 treatment may be partly due to the inhibition of tumor-associated angiogenesis.

Animals↗

PubMed1992

Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin).

We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from tumor cells.

Adult↗

PubMed1992

B30-MDP, a synthetic muramyl dipeptide derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice.

The effect of a muramyl dipeptide derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X-irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30-MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y-ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30-MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1992

DT-5461, a new synthetic lipid A analogue, inhibits lung and liver metastasis of tumor in mice.

We have investigated the antimetastatic effect of a new synthetic lipid A analogue, of low endotoxicity, DT-5461, against two highly metastatic tumor cell lines, L5178Y-ML25 T-lymphoma and B16-BL6 melanoma cells in mice. Four intermittent i.v. administrations of DT-5461 at intervals of 4 days resulted in a significant inhibition of liver metastasis caused by i.v. injection of L5178Y-ML25 cells and lung metastasis of B16-BL6 cells in the experimental metastasis models. Intraperitoneal and intranasal administrations as well as i.v. administration of DT-5461 were also effective in preventing lung metastasis of the melanoma cells. Multiple administrations of DT-5461 before the surgical excision of primary tumors significantly reduced the number of lung colonies of melanoma cells and primary tumor size. Similarly, this treatment modality after the surgical excision of primary tumors showed a greater reduction of lung tumor colonies as compared with lipopolysaccharide, a synthetic lipid A (No. 506) and its analogue as well as untreated control in the spontaneous lung metastasis model. Furthermore, the group that received DT-5461 after the inoculation of lymphoma or melanoma cells showed significantly enhanced survival rate compared with the untreated control. These results suggested that DT-5461 may be therapeutically useful for the inhibition of tumor metastasis.

Animals↗

PubMed1992

Differences in chemotaxis to fibronectin in weakly and highly metastatic tumor cells.

We have examined the chemotactic ability of tumor cell lines with different metastatic potential to plasma fibronectin in Transwell chamber assay. Human renal carcinoma cells with highly metastatic potential, SN12 C-2, chemotactically migrated to fibronectin (10 micrograms/ml) about three-fold more strongly than weakly metastatic SN12 C-4 cells. Similarly, murine melanoma B16-BL6 cells (highly metastatic) showed higher motility to soluble fibronectin in comparison with weakly metastatic B16-F1 cells. Anti-VLA-alpha 3 and beta 1 antibodies potently blocked the chemotaxis of both highly and weakly metastatic cells (SN12 C-2 and C-4) to fibronectin. This implies that the migration of both C-2 and C-4 cells to fibronectin is basically mediated by VLA-3 receptor. In contrast, the anti-VLA-alpha 5 antibody and RGDS peptide significantly inhibited the chemotaxis of SN12 C-2 cells to fibronectin, but did not affect weakly metastatic SN12 C-4 cells. These results suggest that the chemotactic ability to fibronectin positively correlates with the metastatic potential in SN12 and B16 cell lines, and that VLA-5 receptor is concerned in the motility of highly metastatic SN12 C-2 cells to soluble fibronectin.

Antibodies, Monoclonal↗

PubMed1992

Inhibitory anti-tumor effects of interleukin-4 on Philadelphia chromosome-positive acute lymphocytic leukemia and other hematopoietic malignancies.

IL-4 has been shown to possess a broader spectrum of biological activities. Recently, anti-tumor activities of IL-4 on malignant tumors including hematopoietic tumors has been revealed in vitro or in vivo. We investigated the effect of recombinant human (rhIL-4) on the in vitro growth of human leukemia cells and demonstrated the inhibitory anti-tumor activity of rhIL-4 on Ph1-positive ALL cells in association with the decreased activity of cellular tyrosine kinase. This finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibility for patients with Ph1-positive ALL. In this paper, we presented the IL-4-dependent inhibition of Ph1-positive ALL cells and reviewed implications for mechanism of IL-4-dependent inhibition and anti-tumor activities of IL-4.

Antineoplastic Agents↗

PubMed1992

[In vivo effects on human neutrophils by administration of rhG-CSF and clinical significance].

To evaluate the clinical effect by administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin malignant lymphoma (NHL), 17 patients with NHL were subjected to this study. Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts after the cytotoxic chemotherapies and activated neutrophil functions in active oxygen product and expressions of adhesion proteins. To consistent with these results, rhG-CSF administrations post cytotoxic chemotherapy were effective for reducing infection complications associated with neutropenia. Furthermore, administration of rhG-CSF increased peripheral hematopoietic progenitor cells, thus suggesting promising therapeutic potential for autografting. Recently, it has been reported that blood neutrophils may synthesize mRNA and proteins important in inflammation including various cytokines such as IL-1, IL-6, TNF-alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore, the in vitro stimulation by rhG-CSF induced no significant production of these cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and prolonged the overall survival, thus suggesting the hypothesis that use of rhG-CSF in some patients with NHL might control the disease through stimulating both production and functional activation of neutrophils.

Aged↗

PubMed1991

Recombinant human granulocyte colony-stimulating factor inhibits the metastasis of hematogenous and non-hematogenous tumors in mice.

We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.

Animals↗

PubMed1991

Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells.

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.

Cytokines↗

PubMed1991

Inhibition of tumor-induced angiogenesis by sulfated chitin derivatives.

The effect of antimetastatic sulfated chitin derivatives (SCM-chitin III) on angiogenesis induced by B16-BL6 cells was examined in syngeneic mice. SCM-chitin III caused a marked decrease of the number of vessels toward tumor mass (angiogenic response) without affecting the tumor cell growth when coinjected with tumor cells (on day 0), or injected into tumor site on day 1 or 3 after tumor inoculation. In contrast, carboxymethyl chitin as well as heparin had no effect. Invasion of endothelial cells through reconstituted basement membrane (Matrigel) toward tumor-conditioned media was significantly inhibited by SCM-chitin III in a Transwell chamber assay. SCM-chitin III also inhibited the haptotactic migration of endothelial cells to fibronectin-substrate, but did not inhibit the chemotactic activity in tumor conditioned media in vitro. SCM-chitin III did not directly affect the viability and the growth of tumor cells and endothelial cells in vitro. These results suggest that inhibition of lung tumor metastasis by SCM-chitin III may in part be due to the inhibition of tumor-associated angiogenesis.

Animals↗

PubMed1991

Inhibitory effect of fibronectin and its recombinant polypeptides on the adhesion of metastatic melanoma cells to laminin.

We have utilized recombinant fibronectin fragments with cell-binding domain (C-274), heparin-binding domain (H-271) or CS1 peptide in type III connecting segment (IIICS) and their fusion polypeptides such as CH-296 (containing C-274, H-271 and CS1), CH-271 (containing C-274 and H-271) and C-CS1 (containing C-274 and CS1) to investigate the mechanism of the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin as well as fibronectin. These fragments retained cell adhesion-promoting and/or heparin-binding properties when they were immobilized on a surface. Pretreatment of tumor cells with CH-296 or CH-271 suppressed cell adhesion to both laminin and fibronectin. H-271 at the high concentration of 500 micrograms/ml slightly inhibited cell adhesion to laminin (but not to fibronectin), whereas C-274, C-CS1 or a mixture of C-274, H-271 and CS1 (similar molar ratio to CH-296) inhibited cell adhesion to fibronectin but not to laminin. On the other hand, tumor cell adhesion to laminin-substrate was also inhibited by heparin or heparan sulfate, which were able to bind to laminin, suggesting that heparin-like molecules on the cell surface may be included among the laminin receptors. These results indicated that the co-presence of cell- and heparin-binding domains of fibronectin may be required for the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin, and that the interaction of the heparin-binding domain of fibronectin with the cell surface leads to the inhibition of the cell adhesion to laminin.

Amino Acid Sequence↗