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

Abstract

Summary Changes in integrin expression have been shown to be important for the growth and metastatic capacity of melanoma cells. In this study, we have examined the expression of av integrins by three uveal and four cutaneous malanoma lines. No lines expressed avP6 and only TXM1 3, a cutaneous line, expressed av,B8. All lines expressed avf5 and avP3 (four out of four cutaneous, two out of three uveal) or avfi1 (OM431, an uveal line). Thus, OM431 is the second uveal melanoma we have described that expresses avIl and this, we report again, functions as an alternative vitronectin/fibronectin receptor. Subcutaneous growth of cell lines in athymic mice correlated with an avp3-positive, avI1 -negative phenotype. Analysis of clinical material from cutaneous melanoma showed that although av expression was increased in 88% of metastases, this could not all be explained by up-regulation of av,B3, with only 2 out of eight skin metastases expressing this heterodimer.Using antibody SZ.21, which as we report here works in archival material, only 1 out of 15 uveal metastases expressed detectable P3. Thus, acquisition of avP3 expression, which has been implicated in cutaneous melanoma progression, may not be required for development of metastases from uveal melanoma or indeed for skin, as distinct from lymph node, metastases of cutaneous melanoma.Keywords: cell adhesion; ocular melanoma; skin melanoma Cutaneous melanoma is a tumour type whose incidence in Caucasian populations has increased dramatically over the past 80 years. The cancer generally is considered to evolve through a series of distinct pathological steps (Mastrangelo et al, 1985). Thus, melanocytic naevi progress to flat tumours that grow horizontally (radial growth phase, RGP) before they acquire the capacity to invade vertically (vertical growth phase, VGP) and then metastasize. Ocular melanomas, of which the most common are uveal melanomas, occur at about 10% the frequency of cutaneous tumours. These cancers do not seem to progress through the same stages of evolution, but the histological type of uveal melanoma determines the probable metastatic propensity. Thus, the 'spindle' forms rarely metastasize, whereas the 'epithelioid' types are highly metastatic and then usually spread preferentially to the liver (Shields and Shields, 1992).Disseminating cancer cells must interact with the extracellular matrix and this interaction is mediated principally by cell surface adhesion receptors, termed integrins (Hynes, 1992). Integrins are heterodimeric glycoproteins, consisting of a-chains non-covalently associated with ,B-chains, which are expressed at the cell surface. Several studies have examined expression of the integrin family of adhesion molecules in cutaneous melanoma at various stages of tumour development. Levels of expression of different integrin subunits have been reported to increase during tumour progression, including a2,1 (Klein et al, 1991), a3 1 (Natali et al, 1993), a4pl (Schadendorf et al, 1993), a5,Bl (Danen et al, 1994), a6P1 (Natali et al, 1991) ...

Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells

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