ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro

Abstract

Chemotherapy-induced senescence may promote drug resistance and treatment failure. Precise detection and elimination of senescent cancer cells is considered as a novel promising anticancer strategy. However, data on senescence-associated skin cancer cell surface markers as potential therapeutic targets are limited. In the present study, we have established two models of drug-induced senescence in vitro using DNA damaging chemotherapeutics, namely etoposide (0.75-5 µM) and cisplatin (1.25-5 µM), and ten skin cancer cell lines, both melanoma (n = 8, A375, G-361, MM370, SH-4, SK-MEL-1, MeWo, MM127, RPMI-7951) and non-melanoma (n = 2, A431, MCC13), to investigate the levels of 97 cell surface markers. Initial gene expression analysis revealed the increasing tendency in the levels of seven transcripts (ITGA1, ITGA3, VAMP3, STX4, ARMCX3, ULBP2, and PLAUR) and five transcripts (ITGA1, ITGA3, STX4, ARMCX3, and PLAUR) in five etoposide and cisplatin-induced senescent melanoma cell lines, respectively, compared to corresponding proliferating cells. Elevated pools of integrin α1 (ITGA1) were confirmed at mRNA and protein levels in eight drug-induced senescent melanoma cell lines. Similar pattern of changes in integrin α1 levels was not observed in drug-induced senescent non-melanoma skin cancer cells. Analysis using clinical melanoma samples also showed that the levels of ITGA1 and ITGA3 were correlated with the presence of melanoma cells in a section. We document that integrin α1 can be considered as a novel marker of drug-induced senescent melanoma cells. Thus, we postulate that new integrin α1-based targeted therapies can be designed and tested against drug-induced senescent melanoma cells.

Keywords: Drug-induced senescence; Integrin α1 (ITGA1); Melanoma; Senescence-associated cell surface markers.