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ИСТИНА ЦЭМИ РАН |
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Early diagnostics and treatment of prostate cancer (PC) is challenging due to cancer subtype heterogeneity. The critical issue is finding a reliable and sensitive diagnostic/prognostic PC marker. Isoform A of myosin 1C is a promising marker of PC cells that accounts for their invasive phenotype; however its possible feasibility as a diagnostic tool has to be elucidated. Our study aimed to verify the possible correlations between the surface phenotype of PC cells and isoform A expression. We evaluated the expression of isoform A in 4 malignant (PC3, DU145, LNCaP, 22Rv1) and 1 benign (RWPE-1) prostate cell lines both at mRNA (real-time PCR) and protein (western blot, flow cytometry) levels and performed the flow cytometry analysis for 17 surface antigens. We report that all malignant PC cell lines under study were positive for CD29/CD166/CD205 and negative for CD15/CD33/CD34/CD57/CD90/CD133 and CD279. CD10 and CD44 were homogeneously expressed and inversely correlated on PC cell lines, thus exhibiting the inter-subtype heterogeneity. Major expression heterogeneity between cell lines was for CD13, CD16, CD24, CD38, CD54 and CD146, which were differentially expressed not only between cell lines, but also within one cell line (intra-subtype heterogeneity). Correlation analysis revealed that A isoform mRNA expression level strongly correlates with the absence of CD10 (Spearman R coefficient -0.775) and presence of CD13 (R=0.949), CD38 (R=0.800), CD54 (R=0.949) and CD146 (R=0.800). LNCaP cells had the lowest mRNA expression of isoform A (median 0.359) and were CD10+/CD13-/CD38-/CD44-/CD54-/CD146-, while PC3 cells with the highest expression of isoform A ( ) were CD10-/CD13+/CD38+/CD44+/CD54+/CD146+. Thus we report that high and low expression of isoform A is attributed to the distinct tumor phenotypes; these data provide new physiological cues on the role of isoform A of myosin 1C in tumor pathogenesis. This work was supported by RFBR grant # 17-54-33009.