engleski

Integrins αvβ3, αvβ5, α3β1 and α4β1 modulate survival upon cisplatin treatment in MDA-MB-435S breast carcinoma cells

Integrin signaling regulates numerous cellular processes including proliferation, migration, metastasis, cancer-induced angiogenesis, and cell death. The metastatic breast cancer cell line MDA-MB-435S is representative cell line for triple negative breast cancer (TNBC). It has been shown that cisplatin treatment induced response in a subset of patients with TNBC. The aim of this study was to investigate the role of integrins αvβ3, αvβ5, α3β1 and α4β1 expressed on MDA-MB-435S cells in sensitivity to cisplatin. We showed that silencing using β3-specific siRNA decreased the expression of αvβ3, but increased the expression of αvβ5 integrin, while silencing using β5-specific siRNA decreased the expression of αvβ5 but increased the expression of αvβ3 integrin. The αv-specific siRNA decreased expression of both αvβ3 and αvβ5 integrins. Silencing using α3 and α4-specific siRNAs led to decreased expression of integrin heterodimers α3β1 and α4β1, respectively. The reduction of αvβ3 and/or αvβ5, as well as reduction of α3β1 integrin expression decreased MDA-MB-435S cells sensitivity to cisplatin. This result is quite unexpected since our group has shown that de novo expression of αvβ3 confers cisplatin resistance in two other cell lines: laryngeal carcinoma and tongue squamous carcinoma cells. Conversely, the reduction of α4β1 integrin expression increased MDA-MB-435S cells sensitivity to cisplatin. Our results indicate that for αvβ3, αvβ5 or α3β1-positive breast cancer, the combined approach of silencing integrins using αv, β3, β5 or α3-specific siRNAs and cisplatin would act antagonistically. However, for α4β1-positive breast cancer our data suggest the potential for clinical use of α4-specific silencing in sensitization to cisplatin.

integrin ; cisplatin ; breast carcinoma ; survival

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