Role of  V Integrins and Vitronectin in Human Melanoma Cell Growth

Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling Pathway

“…These effects may be a consequence of the ability of integrins to activate a variety of cell-signaling pathways leading to inhibition of apoptosis (71,79). Indeed, the ability of integrins to influence the activity of Rho family GTPases, one of which, RhoC, has been reported to confer metastatic potential on melanoma cells, may be important in this regard (17,18).…”

“…Moreover, in certain circumstances, elevated expression of ␣6-, ␣3-or ␤3-integrins appears to be closely associated with oncogenic transformation and tumor progression. Indeed, there is strong evidence that the expression of ␣v␤3-integrin is tightly correlated with the acquisition of invasive and/or metastatic behavior by melanoma and glioblastoma cells (1,29,32,59,61,71,78). Moreover, ectopic expression of ␣v␤3-integrin in a benign human melanoma cell line can promote invasion and metastasis when tested in a mouse xenograft assay (50).…”

Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3.

“…While Ll-otvl33 interaction may contribute to heterotypic or homotypic cell-cell adhesion, it may be that this interaction is more important for the generation of secondary responses relating to cell motility, survival and growth. Thus, in addition to promoting cell adhesion, otv~ 3 is documented to promote cell migration (Leavesley et al, 1992), suppress apoptosis (Montgomery et al, 1994), and stimulate mitogenesis (Sanders et al, 1992). The interaction between L1 and Otv~ 3 may have significant ramifications for the progression of malignant melanoma and other LI(+) tumors• In this regard, expression of av133 has been directly linked to melanoma progression (Albeda et al, 1991;Albelda, 1993;Montgomery et al, 1994).…”

Anti-integrins as a potential therapeutic target in angiogenesis

“…Integrin αvβ3 expression on melanoma correlates strongly with invasive and metastatic melanoma, and with a poor clinical outcome [39,40]. Integrin αvβ3 contributes to the progression of melanoma by regulating melanoma cell proliferation [50,51] and survival [19], as well as metastasis [37,38,52]. An NPXY sequence in the cytoplasmic tail of the β3 subunit has been shown to play a critical role in mediating the αvβ3 signalling events required for melanoma cell migration and metastasis [53].…”