We utilized gastric cancer cells (GSC1) to demonstrate subversion of nave Mesenchymal Stem Cells (MSC) from adjacent tissue, which are reprogrammed to express a tumor-promoting phenotype, whose cardinal manifestation is to sustain cancer stem cells. Paracrine effects of such primed MSC are sufficient to enable 2D growth of GSC1, while cell-cell interactions are necessary for 3D growth or in vivo tumor formation. Increased expression of R-spondin in primed MSC mediated elevation of Lgr5 expression in GSC1, activation of the WNT/-catenin signaling pathway and translocation of -catenin into the nucleus of most Lgr5 positive cells. Subversion of MSC in the tumor microenvironment (TME) by cancer cells, appears to be a prominent means to sustain the cancer stem cell underpinning of tumor progression. SOURCE: Maty Tzukerman (bimaty@tx.technion.ac.il) - Molecular Medicine Technion

Pluto Bioinformatics

GSE111556: Alteration in gene expression during reprograming of tumor MSC by gastric cancer cells