Abstract 1628: Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts.

Abstract

Abstract One of the main components of the tumor stroma is the cancer-associated fibroblasts (CAFs), which are known to stimulate tumor cell proliferation, angiogenesis and metastasis. Increasing evidence suggests that CAFs also influence the tumor cell response to various treatments. In this study we aimed to characterize the molecular cross-talk between CAFs and head and neck squamous cell carcinoma (HNSCC) cells. Tumor cell lines and CAF cultures were established from tumor biopsies derived from five HNSCC patients at Linköping University Hospital. Patient-matched tumor cells and CAFs were co-cultured for seven days in cell culture flasks, allowing cell-cell contact. After cell sorting the gene expression in mono-cultured and co-cultured tumor cells was investigated by Affymetrix microarray. Molecular networks were analyzed by Ingenuity Pathway Analysis (IPA). The expression of selected genes was verified by quantitative real-time PCR (qPCR) analysis. Fiftyeight genes were found to be differentially expressed (q<0.05) in tumor cells co-cultured with CAFs when compared to tumor cells in mono-culture. The top functions of these genes were cancer, cellular movement, and embryonic development as analyzed by IPA. Four genes (POSTN, GREM1, COL1A2, and COL6A3) were upregulated by more than 2-fold while 14 genes were found to be downregulated by at least 50%. The four upregulated genes have all been associated with epithelial-to-mesenchymal transition (EMT), increased migration, and TGFβ-pathway signaling. By qPCR analysis the expression of POSTN, GREM1 and COL1A2 was found to be induced by several hundred-fold in some of the cell lines under co-culture conditions. There were no significant changes in the expression of these genes when tumor cells and CAFs were co-cultured in a trans-well system, suggesting that the effect may be contact-dependent. Functional analyses are now being performed to determine the importance of these findings. Citation Format: Anna Ansell, Matti Kankainen, Outi Monni, Ann-Charlotte Johansson. Molecular cross-talk between head and neck squamous cell carcinoma cells and cancer-associated fibroblasts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1628. doi:10.1158/1538-7445.AM2013-1628