Invasive and noninvasive uveal melanomas have different adhesive properties

Abstract

Aims To establish if invasive and noninvasive uveal melanomas have differences in expression of adhesion molecules, and whether their adhesive interactions with the extracellular matrix (ECM) and endothelium vary. Methods Cells from an invasive and noninvasive uveal melanoma cell line and hepatic and dermal microvascular endothelial cells were assessed by flow cytometry for adhesion molecule expression. Tumour cell adhesion to ECM substrates (collagens I and IV, fibronectin, laminin, and vitronectin) and endothelial cells was also investigated using a commercially available assay or a fluorescencebased in vitro assay, respectively. The significance of results comparing cell lines was determined using a Student's t-test, whereby P-values of less than 0.05 were taken as significant. Results a1-and a4-integrins were not expressed by noninvasive cells, but were detected on invasive cells. The invasive cell line also expressed higher levels of other integrins than the noninvasive line. Correspondingly, invasive cells adhered in higher numbers to ECM substrates and endothelial cells, and for the latter, the difference was highly significant (Po0.001). No preference in adhesion of invasive cells for the hepatic endothelium was observed. Conclusions Successful attachment to and migration through the ECM, basement membrane, and endothelium are vital processes involved in malignant progression. Differential expression of a1-and a4-integrins by invasive and noninvasive cells infers a role for these receptors in invasion, while the ability of invasive cells to adhere more efficiently to the endothelium suggests that this is a critical factor in uveal melanoma invasion.

The insulin‐like growth factor‐I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells

“…One early step is cell adhesion (through integrins at the cell surface) to ECM components. It was recently shown that a1, a2, and a3 integrins showed higher expression in uveal melanoma cells with invasive phenotype compared with noninvasive cells, and inhibition of these a integrins decreased binding to collagen IV, fibronectin, and laminin (Woodward et al. 2005).…”

Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma

“…Although uveal melanomas have been reported to express a range of adhesion molecules, including integrins and members of the immunoglobulin family [5,6,[35][36][37][38], little is known about how adhesion protein expression may influence the invasion process in this tumor type. Moreover, it is unclear whether the same mechanisms important in cutaneous melanoma are equally relevant in uveal melanoma, or whether different interactions are required [39]. We observed an increase in ITGA8 within the more invasive group of uveal cell lines, whereas expression of ITGA6 and ITGB8 was decreased.…”

“…Seftor et al [4] described the involvement of high expression of laminin 5 and several members of the matrix metalloproteinase family in uveal melanoma progression. Additionally, uveal melanomas have been found to express more integrins than normal uveal melanocytes or spindle cell tumors that have a less aggressive and invasive phenotype [5,6]. [8][9][10][11][12][13], as well as phenotypic characteristics of these tumors such as invasive ability [10][11][12][13].…”

A Web-based database of genetic association studies in cutaneous melanoma enhanced with network-driven data exploration tools

“…Finally, proteins encoded by ITGA7 and ITGA9 genes belong to the integrin alpha chain family. Changes in integrins expression have been reported during the malignant progression of many tumors, and much evidence exists implicating their involvement in CM metastasis (21). Malacards also implicates ITGA7 and ITGA9 in CM (eighth and third rank of gene-related diseases, respectively).…”