Abstract 1513: Mesenchymal stromal cells enhance the malignant potential of human colorectal cancer cells by inducing epithelial to mesenchymal transition-related phenomena

Abstract

Abstract Background: Mesenchymal stromal cells (MSCs) are recruited to primary and metastatic sites of several tumour types, including colorectal cancer (CRC), and might contribute to tumour progression. The actual role played by MSCs and the mechanisms underlying MSC-tumour interactions remain to be clarified. We investigated the effects of human bone-marrow-derived MSCs (BM-MSCs) on CRC, in vitro and in vivo. Material and methods: Human established CRC cell lines were cultured in the presence or absence of BM-MSCs, in direct contact or in transwell plates. After a five day culture, tumour cell proliferation was assessed by differential cell counts, surface molecule expression was analyzed by flow cytometry, and production of soluble factors in culture supernatants was measured by Raybio antibody array® and ELISA. Tumour cells, sorted upon co-culture by flow cytometry, were evaluated for the expression of epithelial to mesenchymal transition (EMT)-related genes by quantitative PCR and for in vitro invasiveness, by chemoinvasion assay. Furthermore, their tumorigenicity was assessed upon injection in NOD/SCID mice and developing tumours were analyzed by immunofluorescence. Results: MSCs significantly increased tumour cell proliferation and decreased CD44 expression, independently of cell-to-cell contact. Analysis of co-culture supernatants revealed higher amounts of IL-6, MCP-1, RANTES and Angiogenin, in comparison to supernatants derived from single cultures. Moreover increased expression of several EMT-related genes, including SNAI2, TWIST, N-Cadherin, was detected on CRC cells sorted upon co-culture as compared with controls. Importantly, CRC cells co-cultured with MSCs showed higher invasive behaviour in vitro, than CRC cells cultured alone. No significant changes were observed in tumorigenicity. However, tumours originated from tumour cells co-cultured with MSCs showed a significantly higher vessel density as compared to controls. Conclusions: MSCs reduce adhesiveness, induce expression of EMT-related genes and increase proliferation, invasiveness and angiogenic potential of CRC cells. These effects might contribute to CRC progression and spreading. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1513. doi:10.1158/1538-7445.AM2011-1513