Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

Abstract

We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs) migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT)–related genes such as fibronectin (FN), SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

The interplay between adipose-derived stem cells and bladder cancer cells

“…fibronectin, SPARC, and galectin 1 in colon cancer cells (KM12SM). Interestingly, their expression was not elevated in cancer cells indirectly co-cultured with MSCs 67 .…”

Mathematical modeling of metastasis, a feasible way to detect the weakness

“…These cells begin to make the phenotype change due to external factors, such as the effect of the microenvironment [28] and/or interaction with the immune system [29] . In 2017 Takigawa et al [30] stated that mesenchymal stem cells induce epithelial to mesenchymal transition in colon cancer cells through direct cell-to-cell contact.…”

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

“…Two findings in the current study were surprising: direct transfer of cellular material from TAMRA+ cells to CD90+ MSCs and fusion of two cells of the same type that captured either TAMRA DNA or CD90 antibodies. There are studies demonstrating the direct contacts between MSCs and other cell types, including cancer cells [51][52][53][54][55][56], and providing evidence of direct physical transfer of cellular material from one cell to another [53,[57][58][59][60][61], up to complete fusion (cellular cannibalism or entosis) [62,63]. The mechanisms of these interactions are almost unexplored.…”