The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
James B Mccarthy - One of the best experts on this subject based on the ideXlab platform.
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a role of chondroitin sulfate glycosaminoglycan binding site in α4β1 integrin mediated Melanoma Cell adhesion
Journal of Biological Chemistry, 1998Co-Authors: Joji Iida, Theodore R Oegema, Alexandra M L Meijne, Ted A Yednock, Nicholas L Kovach, Leo T Furcht, James B MccarthyAbstract:We have previously reported that alpha4beta1 (but not alpha5beta1) integrin-mediated Melanoma Cell adhesion is inhibited by removal of Cell surface chondroitin sulfate glycosaminoglycan (CSGAG), suggesting that Melanoma chondroitin sulfate proteoglycan plays a role in modulating the adhesive function of alpha4beta1 integrin. In the current study, we demonstrated that alpha4beta1 integrin binds to CSGAG. We have identified a peptide from within alpha4 integrin termed SG1 (KKEKDIMKKTI) that binds to Cell surface Melanoma chondroitin sulfate proteoglycan, indicating that SG1 represents a CSGAG binding site within the alpha4 integrin subunit. Soluble SG1 inhibits alpha4beta1 integrin-mediated human Melanoma Cell adhesion to CS1. Polyclonal antibody generated against the peptide inhibits Melanoma Cell adhesion to CS1, and the inhibition is reversed by Mn2+ and an activating monoclonal antibody anti-beta1 (8A2). Additionally, pretreatment of Cells with anti-SG1 IgG inhibits the expression of the monoclonal antibody 15/7 epitope in the presence of soluble CS1 peptide, suggesting that anti-SG1 IgG prevents ligand binding by alpha4beta1 integrin. These results demonstrate that alpha4beta1 integrin interacts directly with CSGAG through SG1 site, and that this site can affect the ligand binding properties of the integrin.
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cd44 chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human Melanoma Cell migration on type iv collagen and invasion of basement membranes
Molecular Biology of the Cell, 1996Co-Authors: Jennifer R Knutson, Joji Iida, Gregg B Fields, James B MccarthyAbstract:Tumor Cell invasion of basement membranes (BM) represents one of the critical steps in the metastatic process. Tumor Cell recognition of individual BM matrix components may involve individual Cell adhesion receptors, such as integrins or Cell surface proteoglycans, or may involve a coordinate action of both types of receptors. In this study, we have focused on the identification of a Cell surface CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human Melanoma Cells that are both directly involved in the in vitro invasion of reconstituted BM via a type IV collagen-dependent mechanism. Interfering with Cell surface expression of human Melanoma CSPG with either p-nitro-phenyl-beta-D-xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation (mAb) preincubation inhibits Melanoma Cell invasion through reconstituted BM. These treatments also strongly inhibit Melanoma Cell migration on type IV collagen, however, they are ineffective at inhibiting Cell adhesion to type IV collagen. Purified Melanoma Cell surface CD44/CSPG, or purified chondroitin sulfate, bind to type IV collagen affinity columns, consistent with a role for CD44/CSPG-type IV collagen interactions in mediating tumor Cell invasion. In contrast, Melanoma Cell migration on laminin (LM) does not involve CD44/CSPG, nor does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1 integrin mAbs are capable of blocking Melanoma Cell invasion of reconstituted BM. Both of these anti-integrin mAbs inhibit Melanoma Cell adhesion and migration on type IV collagen, whereas only anti-beta 1 mAb inhibits Cell adhesion to LM. Collectively, these results indicate that Melanoma Cell adhesion to type IV collagen is an important consideration in invasion of reconstituted BM in vitro, and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote human Melanoma Cell adhesion, migration, and invasion in vivo.
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coordinate role for Cell surface chondroitin sulfate proteoglycan and alpha 4 beta 1 integrin in mediating Melanoma Cell adhesion to fibronectin
Journal of Cell Biology, 1992Co-Authors: Joji Iida, Leo T Furcht, Amy E N Skubitz, E A Wayner, James B MccarthyAbstract:Cellular recognition and adhesion to the extraCellular matrix (ECM) has a complex molecular basis, involving both integrins and Cell surface proteoglycans (PG). The current studies have used specific inhibitors of chondroitin sulfate proteoglycan (CSPG) synthesis along with anti-alpha 4 integrin subunit monoclonal antibodies to demonstrate that human Melanoma Cell adhesion to an A-chain derived, 33-kD carboxyl-terminal heparin binding fragment of human plasma fibronectin (FN) involves both Cell surface CSPG and alpha 4 beta 1 integrin. A direct role for Cell surface CSPG in mediating Melanoma Cell adhesion to this FN fragment was demonstrated by the identification of a cationic synthetic peptide, termed FN-C/H-III, within the fragment. FN-C/H-III is located close to the amino terminal end of the fragment, representing residues #1721-1736 of intact FN. FN-C/H-III binds CSPG directly, can inhibit CSPG binding to the fragment, and promotes Melanoma Cell adhesion by a CSPG-dependent, alpha 4 beta 1 integrin-independent mechanism. A scrambled version of FN-C/H-III does not inhibit CSPG binding or Cell adhesion to the fragment or to FN-C/H-III, indicating that the primary sequence of FN-C/H-III is important for its biological properties. Previous studies have identified three other synthetic peptides from within this 33-kD FN fragment that promote Cell adhesion by an arginyl-glycyl-aspartic acid (RGD) independent mechanism. Two of these synthetic peptides (FN-C/H-I and FN-C/H-II) bind heparin and promote Cell adhesion, implicating Cell surface PG in mediating Cellular recognition of these two peptides. Additionally, a third synthetic peptide, CS1, is located in close proximity to FN-C/H-I and FN-C/H-II and it promotes Cell adhesion by an alpha 4 beta 1 integrin-dependent mechanism. In contrast to FN-C/H-III, Cellular recognition of these three peptides involved contributions from both CSPG and alpha 4 integrin subunits. Of particular importance are observations demonstrating that CS1-mediated Melanoma Cell adhesion could be inhibited by interfering with CSPG synthesis or expression. Since CS1 does not bind CSPG, the results suggest that CSPG may modify the function and/or activity of alpha 4 beta 1 integrin on the surface of human Melanoma Cells. Together, these results support a model in which the PG and integrin binding sites within the 33-kD fragment may act in concert to focus these two Cell adhesion receptors into close proximity on the Cell surface, thereby influencing initial Cellular recognition events that contribute to Melanoma Cell adhesion on this fragment.
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a Cell surface chondroitin sulfate proteoglycan immunologically related to cd44 is involved in type i collagen mediated Melanoma Cell motility and invasion
Journal of Cell Biology, 1992Co-Authors: Anne E Faassen, J A Schrager, David J Klein, Theodore R Oegema, J R Couchman, James B MccarthyAbstract:The metastatic spread of tumor Cells occurs through a complex series of events, one of which involves the adhesion of tumor Cells to extraCellular matrix (ECM) components. Multiple interactions between Cell surface receptors of an adherent tumor Cell and the surrounding ECM contribute to Cell motility and invasion. The current studies evaluate the role of a Cell surface chondroitin sulfate proteoglycan (CSPG) in the adhesion, motility, and invasive behavior of a highly metastatic mouse Melanoma Cell line (K1735 M4) on type I collagen matrices. By blocking mouse Melanoma Cell production of CSPG with p-nitrophenyl beta-D-xylopyranoside (beta-D-xyloside), a compound that uncouples chondroitin sulfate from CSPG core protein synthesis, we observed a corresponding decrease in Melanoma Cell motility on type I collagen and invasive behavior into type I collagen gels. Melanoma Cell motility on type I collagen could also be inhibited by removing Cell surface chondroitin sulfate with chondroitinase. In contrast, type I collagen-mediated Melanoma Cell adhesion and spreading were not affected by either beta-D-xyloside or chondroitinase treatments. These results suggest that mouse Melanoma CSPG is not a primary Cell adhesion receptor, but may play a role in Melanoma Cell motility and invasion at the level of Cellular translocation. Furthermore, purified mouse Melanoma Cell surface CSPG was shown, by affinity chromatography and in solid phase binding assays, to bind to type I collagen and this interaction was shown to be mediated, at least in part, by chondroitin sulfate. Additionally we have determined that mouse Melanoma CSPG is composed of a 110-kD core protein that is recognized by anti-CD44 antibodies on Western blots. Collectively, our data suggests that interactions between a Cell surface CD44-related CSPG and type I collagen in the ECM may play an important role in mouse Melanoma Cell motility and invasion, and that the chondroitin sulfate portion of the proteoglycan seems to be a critical component in mediating this effect.
Eyal Greenberg - One of the best experts on this subject based on the ideXlab platform.
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ceacam1 promotes Melanoma Cell growth through sox 2
Neoplasia, 2014Co-Authors: Rona Ortenberg, Sivan Sapoznik, Gilli Galorehaskel, Ilanit Greenberg, Bella Zamlin, Eyal GreenbergAbstract:The prognostic value of the carcinoembryonic antigen Cell adhesion molecule 1 (CEACAM1) in Melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that interCellular homophilic CEACAM1 interactions protect Melanoma Cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on Melanoma Cell biology. By employing tissue microarrays and low-passage primary cultures of metastatic Melanoma, we show that CEACAM1 expression gradually increases from nevi to metastatic specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using experimental systems of CEACAM1 knockdown and overexpression of selective variants or truncation mutants, we prove that only the full-length long tail variant enhances Melanoma Cell proliferation in vitro and in vivo. This effect is not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated by interCellular homophilic interactions. Downstream, CEACAM1-Long increases the expression of Sox-2, which we show to be responsible for the CEACAM1-mediated enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's activity compared with the consensus nucleotides. Importantly, case-control genetic SNP analysis of 134 patients with Melanoma and matched healthy donors show that patients with Melanoma do not exhibit the Hardy-Weinberg balance and that homozygous SNP genotype enhances the hazard ratio to develop Melanoma by 35%. These observations shed new mechanistic light on the role of CEACAM1 in Melanoma, forming the basis for development of novel therapeutic and diagnostic technologies.
Martine J Jager - One of the best experts on this subject based on the ideXlab platform.
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uveal Melanoma Cell lines where do they come from an american ophthalmological society thesis
Transactions of the American Ophthalmological Society, 2016Co-Authors: Martine J Jager, Antonio Bermudez J Magner, Bruce R Ksander, Sander R DubovyAbstract:PURPOSE: To determine whether some of the most often used uveal Melanoma Cell lines resemble their original tumor. METHODS: Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on Cell lines and their primary tumors. We examined five Cell lines and the primary tumors from which they were derived. RESULTS: Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One Cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five Cell lines showed disomy 3 and BAP1 expression. All of the Cell lines had gain of 8q. Two Cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. CONCLUSIONS: All Cell lines could be traced back to their original uveal Melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal Melanoma Cell lines.
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© 2008 Molecular Vision Triamcinolone acetonide and anecortave acetate do not stimulate uveal Melanoma Cell growth
2013Co-Authors: Mariam El Filali, Irene Homminga, Willem Maat, Pieter A. Van Der Velden, Martine J JagerAbstract:Purpose: Radiotherapy-induced radiation retinopathy can develop in over 40 % of eyes treated for uveal Melanoma. Triamcinolone acetonide (TA) and anecortave acetate (AA) can be used to treat radiation retinopathy. It is not known whether TA or AA has any effect on potentially still viable uveal Melanoma Cells in the choroid after radiotherapy. We therefore studied the effect of these drugs on the proliferation of uveal Melanoma Cell lines in vitro. Furthermore, as these drugs are supposed to counteract vascular leakage, we determined their effect on the expression and production of the proangiogenic vascular endothelial growth factor-A (VEGF-A), the antiangiogenic pigment epithelium-derived factor (PEDF), and thrombospondin-1 (TSP-1) in uveal Melanoma Cells. Methods: Three uveal Melanoma Cell lines were treated in vitro with TA or AA. Cell proliferation was measured by counting Cells and using the Water-Soluble Tetrazolium Salt-1 (WST-1) assay. VEGF-A and PEDF production was measured by ELISA, and intraCellular expression of angiogenic-associated genes including VEGF-A, PEDF, and TSP-1 was determined by real-time quantitative RT–PCR. Results: We found no effect of TA or AA on tumor Cell growth or production of VEGF-A and PEDF in any of the three uveal Melanoma Cell lines tested. Regarding expression as measured by RT–PCR, TA had an inhibiting effect on TSP-1 in only one Cell line, and no effect on VEGF-A or PEDF. AA showed a similar lack of effect. Conclusions: Since TA and AA do not stimulate uveal Melanoma Cell growth, it seems to be safe to use these drugs t
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Triamcinolone acetonide and anecortave acetate do not stimulate uveal Melanoma Cell growth.
Molecular vision, 2008Co-Authors: Mariam El Filali, Irene Homminga, Willem Maat, Pieter A. Van Der Velden, Martine J JagerAbstract:Purpose Radiotherapy-induced radiation retinopathy can develop in over 40% of eyes treated for uveal Melanoma. Triamcinolone acetonide (TA) and anecortave acetate (AA) can be used to treat radiation retinopathy. It is not known whether TA or AA has any effect on potentially still viable uveal Melanoma Cells in the choroid after radiotherapy. We therefore studied the effect of these drugs on the proliferation of uveal Melanoma Cell lines in vitro. Furthermore, as these drugs are supposed to counteract vascular leakage, we determined their effect on the expression and production of the proangiogenic vascular endothelial growth factor-A (VEGF-A), the antiangiogenic pigment epithelium-derived factor (PEDF), and thrombospondin-1 (TSP-1) in uveal Melanoma Cells. Methods Three uveal Melanoma Cell lines were treated in vitro with TA or AA. Cell proliferation was measured by counting Cells and using the Water-Soluble Tetrazolium Salt-1 (WST-1) assay. VEGF-A and PEDF production was measured by ELISA, and intraCellular expression of angiogenic-associated genes including VEGF-A, PEDF, and TSP-1 was determined by real-time quantitative RT-PCR. Results We found no effect of TA or AA on tumor Cell growth or production of VEGF-A and PEDF in any of the three uveal Melanoma Cell lines tested. Regarding expression as measured by RT-PCR, TA had an inhibiting effect on TSP-1 in only one Cell line, and no effect on VEGF-A or PEDF. AA showed a similar lack of effect. Conclusions Since TA and AA do not stimulate uveal Melanoma Cell growth, it seems to be safe to use these drugs to treat radiation retinopathy after irradiation for uveal Melanoma. Additional experiments using more Cell lines or primary tumor Cell cultures are needed to validate this conclusion. Furthermore, the results of our study suggest that TA does not exert its antileakage effect through downregulation of VEGF-A or upregulation of TSP-1 or PEDF in uveal Melanoma Cell lines. It is possible that TA and AA influence these pro- and antiangiogenic factors only under hypoxic circumstances. Further investigation is needed.
Rona Ortenberg - One of the best experts on this subject based on the ideXlab platform.
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ceacam1 promotes Melanoma Cell growth through sox 2
Neoplasia, 2014Co-Authors: Rona Ortenberg, Sivan Sapoznik, Gilli Galorehaskel, Ilanit Greenberg, Bella Zamlin, Eyal GreenbergAbstract:The prognostic value of the carcinoembryonic antigen Cell adhesion molecule 1 (CEACAM1) in Melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that interCellular homophilic CEACAM1 interactions protect Melanoma Cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on Melanoma Cell biology. By employing tissue microarrays and low-passage primary cultures of metastatic Melanoma, we show that CEACAM1 expression gradually increases from nevi to metastatic specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using experimental systems of CEACAM1 knockdown and overexpression of selective variants or truncation mutants, we prove that only the full-length long tail variant enhances Melanoma Cell proliferation in vitro and in vivo. This effect is not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated by interCellular homophilic interactions. Downstream, CEACAM1-Long increases the expression of Sox-2, which we show to be responsible for the CEACAM1-mediated enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's activity compared with the consensus nucleotides. Importantly, case-control genetic SNP analysis of 134 patients with Melanoma and matched healthy donors show that patients with Melanoma do not exhibit the Hardy-Weinberg balance and that homozygous SNP genotype enhances the hazard ratio to develop Melanoma by 35%. These observations shed new mechanistic light on the role of CEACAM1 in Melanoma, forming the basis for development of novel therapeutic and diagnostic technologies.
Joji Iida - One of the best experts on this subject based on the ideXlab platform.
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a role of chondroitin sulfate glycosaminoglycan binding site in α4β1 integrin mediated Melanoma Cell adhesion
Journal of Biological Chemistry, 1998Co-Authors: Joji Iida, Theodore R Oegema, Alexandra M L Meijne, Ted A Yednock, Nicholas L Kovach, Leo T Furcht, James B MccarthyAbstract:We have previously reported that alpha4beta1 (but not alpha5beta1) integrin-mediated Melanoma Cell adhesion is inhibited by removal of Cell surface chondroitin sulfate glycosaminoglycan (CSGAG), suggesting that Melanoma chondroitin sulfate proteoglycan plays a role in modulating the adhesive function of alpha4beta1 integrin. In the current study, we demonstrated that alpha4beta1 integrin binds to CSGAG. We have identified a peptide from within alpha4 integrin termed SG1 (KKEKDIMKKTI) that binds to Cell surface Melanoma chondroitin sulfate proteoglycan, indicating that SG1 represents a CSGAG binding site within the alpha4 integrin subunit. Soluble SG1 inhibits alpha4beta1 integrin-mediated human Melanoma Cell adhesion to CS1. Polyclonal antibody generated against the peptide inhibits Melanoma Cell adhesion to CS1, and the inhibition is reversed by Mn2+ and an activating monoclonal antibody anti-beta1 (8A2). Additionally, pretreatment of Cells with anti-SG1 IgG inhibits the expression of the monoclonal antibody 15/7 epitope in the presence of soluble CS1 peptide, suggesting that anti-SG1 IgG prevents ligand binding by alpha4beta1 integrin. These results demonstrate that alpha4beta1 integrin interacts directly with CSGAG through SG1 site, and that this site can affect the ligand binding properties of the integrin.
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cd44 chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human Melanoma Cell migration on type iv collagen and invasion of basement membranes
Molecular Biology of the Cell, 1996Co-Authors: Jennifer R Knutson, Joji Iida, Gregg B Fields, James B MccarthyAbstract:Tumor Cell invasion of basement membranes (BM) represents one of the critical steps in the metastatic process. Tumor Cell recognition of individual BM matrix components may involve individual Cell adhesion receptors, such as integrins or Cell surface proteoglycans, or may involve a coordinate action of both types of receptors. In this study, we have focused on the identification of a Cell surface CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human Melanoma Cells that are both directly involved in the in vitro invasion of reconstituted BM via a type IV collagen-dependent mechanism. Interfering with Cell surface expression of human Melanoma CSPG with either p-nitro-phenyl-beta-D-xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation (mAb) preincubation inhibits Melanoma Cell invasion through reconstituted BM. These treatments also strongly inhibit Melanoma Cell migration on type IV collagen, however, they are ineffective at inhibiting Cell adhesion to type IV collagen. Purified Melanoma Cell surface CD44/CSPG, or purified chondroitin sulfate, bind to type IV collagen affinity columns, consistent with a role for CD44/CSPG-type IV collagen interactions in mediating tumor Cell invasion. In contrast, Melanoma Cell migration on laminin (LM) does not involve CD44/CSPG, nor does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1 integrin mAbs are capable of blocking Melanoma Cell invasion of reconstituted BM. Both of these anti-integrin mAbs inhibit Melanoma Cell adhesion and migration on type IV collagen, whereas only anti-beta 1 mAb inhibits Cell adhesion to LM. Collectively, these results indicate that Melanoma Cell adhesion to type IV collagen is an important consideration in invasion of reconstituted BM in vitro, and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote human Melanoma Cell adhesion, migration, and invasion in vivo.
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coordinate role for Cell surface chondroitin sulfate proteoglycan and alpha 4 beta 1 integrin in mediating Melanoma Cell adhesion to fibronectin
Journal of Cell Biology, 1992Co-Authors: Joji Iida, Leo T Furcht, Amy E N Skubitz, E A Wayner, James B MccarthyAbstract:Cellular recognition and adhesion to the extraCellular matrix (ECM) has a complex molecular basis, involving both integrins and Cell surface proteoglycans (PG). The current studies have used specific inhibitors of chondroitin sulfate proteoglycan (CSPG) synthesis along with anti-alpha 4 integrin subunit monoclonal antibodies to demonstrate that human Melanoma Cell adhesion to an A-chain derived, 33-kD carboxyl-terminal heparin binding fragment of human plasma fibronectin (FN) involves both Cell surface CSPG and alpha 4 beta 1 integrin. A direct role for Cell surface CSPG in mediating Melanoma Cell adhesion to this FN fragment was demonstrated by the identification of a cationic synthetic peptide, termed FN-C/H-III, within the fragment. FN-C/H-III is located close to the amino terminal end of the fragment, representing residues #1721-1736 of intact FN. FN-C/H-III binds CSPG directly, can inhibit CSPG binding to the fragment, and promotes Melanoma Cell adhesion by a CSPG-dependent, alpha 4 beta 1 integrin-independent mechanism. A scrambled version of FN-C/H-III does not inhibit CSPG binding or Cell adhesion to the fragment or to FN-C/H-III, indicating that the primary sequence of FN-C/H-III is important for its biological properties. Previous studies have identified three other synthetic peptides from within this 33-kD FN fragment that promote Cell adhesion by an arginyl-glycyl-aspartic acid (RGD) independent mechanism. Two of these synthetic peptides (FN-C/H-I and FN-C/H-II) bind heparin and promote Cell adhesion, implicating Cell surface PG in mediating Cellular recognition of these two peptides. Additionally, a third synthetic peptide, CS1, is located in close proximity to FN-C/H-I and FN-C/H-II and it promotes Cell adhesion by an alpha 4 beta 1 integrin-dependent mechanism. In contrast to FN-C/H-III, Cellular recognition of these three peptides involved contributions from both CSPG and alpha 4 integrin subunits. Of particular importance are observations demonstrating that CS1-mediated Melanoma Cell adhesion could be inhibited by interfering with CSPG synthesis or expression. Since CS1 does not bind CSPG, the results suggest that CSPG may modify the function and/or activity of alpha 4 beta 1 integrin on the surface of human Melanoma Cells. Together, these results support a model in which the PG and integrin binding sites within the 33-kD fragment may act in concert to focus these two Cell adhesion receptors into close proximity on the Cell surface, thereby influencing initial Cellular recognition events that contribute to Melanoma Cell adhesion on this fragment.