Integrin expression in human melanoma cell lines: Heterogeneity of vitronectin receptor composition and function

Abstract

Ten human melanoma cell lines were examined for integrin-receptor expression using a panel of antibodies directed against different integrin subunits. Considerable heterogeneity was detected for levels of expression of 7 integrins, including the alpha v beta 3 vitronectin receptor where a correlation between tumorigenic capacity in athymic nude mice and alpha v beta 3 levels was found. Detailed analysis of the vitronectin receptor on these lines revealed heterogeneity of composition. In one cell line, VUP, an alpha v beta 1 association was detected and, by antibody-inhibition studies, this receptor was shown to bind vitronectin as its ligand. In another line, DX3, evidence was obtained which indicated that apart from the alpha v beta 3 receptor the alpha v was able to associate with another beta subunit which was not beta 3. The existence of these alternative forms of the vitronectin receptor in this small sample of tumours of common origin might explain why the capacity to bind to fibrinogen and vitronectin substrates by these cells did not necessarily correlate with alpha v beta 3 levels.

Comparative analysis of integrins in vitro and in vivo in uveal and cutaneous melanomas

“…Immunoprecipitation with antibody to av (13C2) coprecipitated a (1-sized band from both OM431 and V(+)B2 but not from the SP6.5 or OCM-I cell lines. It appears that OM431 is the second uveal melanoma cell line that we have shown to lack avP3 but to express avil (Marshall et al, 1991). Figure 1 also confirms the flow cytometry data ( Table 2) that avP5 is expressed weakly by OM431, SP6.5, OCM-I and, as reported previously, V + B2 (Marshall, 1995).…”

“…In contrast the av,B1-positive lines were either poorly or non-tumorigenic. In addition, using flow cytometry we have measured expression of av,5, avP6 and avP8 on the nine cutaneous melanoma cell lines already examined for av,B3 expression (Marshall et al, 1991). Together with the data reported here, we have found that formation of subcutaneous xenografts by 17 human (cutaneous and uveal) melanoma lines correlates with an avP3-positive, av,B1-negative phenotype.…”

“…The avo-heterodimers expressed by four uveal melanoma-derived cell lines, V(+)B2, OM431, OCM-I and SP6.5, were analysed by immunoprecipitation of surface-iodinated, NP40-detergent-lysed cell extracts as described previously (Marshall et al, 1991 Immunoprecipitation of uveal melanoma av-integrins SP6.5, OCM1 and OM431 uveal lines and, for comparison, the VUP-derived subline V + B2 were analysed by immunoprecipitation. Figure 1 shows that both SP6.5 and OCM-1 express av03…”

“…Earlier studies by Boukerche and colleagues (1994) showed that the co-injection of antibody LYP18, which cross-reacts with both aIIb133 and avP3, inhibited tumour growth of the human melanoma cell line M3Dau (Boukerche et al, 1989). We have shown that the ability of human melanoma cell lines to form subcutaneous tumours in athymic nude mice correlated with levels of expression of avP3 (Marshall et al, 1991). However, av,3-negative cutaneous melanoma cell lines have metastasized in nude mice (Boukerche et al, 1994;Danen et al, 1995), suggesting that expression of this heterodimer is not obligatory for malignant behaviour.…”

Pentoxifylline modulates cell surface integrin expression and integrin mediated adhesion of B16F10 cells to extracellular matrix components

“…A correlation has been reported between increased expression of avb3 and aIIbb3 integrins and increased invasive and metastatic potential of melanoma cells. 13,14 Modulation of a5 integrin has been shown to be involved in tumor progression and metastasis, but its role is still not very clear. High levels of a5 expressions was shown to be negatively correlated with the progression of many carcinomas including breast carcinoma and melanoma.…”