Tumor Specific Recruitment and Reprograming of Mesenchymal Stem Cells in Tumorigenesis

Non-neoplastic stromal cells harvested from patient tumors were identified as tumor-derived Mesenchymal Stem Cells (MSC) by their multi-potential capacity to differentiate into adipocytes, osteoblasts and chondrocytes and by the expression of MSC specific cell surface markers. These procedures yielded also epithelial cancer cells and their counterpart MSC from gastric carcinoma (GSC1) and lung carcinoma (LC2). While the LC2 cancer cell growth is independent of their LC-MSC, the GSC1 cancer cell growth is critically dependent on the presence of their counterpart GSC-MSC or their conditioned medium (CM). The fact that none of the various other tumor-derived MSC were able to restore the specific effect of GSC-MSC on GSC1 cancer cell growth suggests specificity of tumor-derived MSC, which are specifically recruited and `educated`/reprogrammed by the cancer cells to support tumor growth. Using cytokine array analysis, we were able to demonstrate that GSC1 cell growth is mediated through HGF/c-MET signaling pathway which is activated exclusively by HGF secreted from GSC-MSC. An innovative approach demonstrates GSC1-mediated specific tropism of `naïve` MSC from the adjacent tissue in a tumor specific manner to support tumor progression. The results suggest that specific tumor tropic `naïve` MSC are reprogrammed in a tumor-specific manner to support gastric tumor progression. Understanding the mechanisms involved in the interactions of the tumor cancer cells and tumor-derived MSC will constitute the basis for developing multimodal anti-cancer therapeutic strategies that will also take into account the specific tumor tropism properties of MSC and their reprogramming.