Mesenchymal stem cells: key players in cancer progression

Abstract

Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour. The key question is how they interact there. MSCs may interact with tumour cells through paracrine signalling. On the other hand, MSCs have the capacity to differentiate to various cell types such as osteocytes, chondrocytes and adipocytes and it is possible that MSCs differentiate at the site of the tumour. More recently it has been shown that cross-talk between tumour cells and MSCs has been shown to increase metastatic potential and promote epithelial-to-mesenchymal transition. This review will focus on the role of MSCs in tumour development at various stages of progression from growth of the primary tumour to the establishment of distant metastasis.

Keywords: Cancer progression; Mesenchymal stem cells; Tumour metastasis; Tumour microenvironment; Tumour stroma.

Fig. 1

MSC and tumour cell interaction in cancer progression. MSCs have been shown to interact with tumour cells at the primary site and during metastatic colonisation in a manner that promotes cancer progression. MSCs have been shown to promote EMT in tumour cells through direct cell-cell contact, which could in part be due to TGFβ secretion [38, 82]. Additionally, tumour cell secretion of osteopontin (OPN) was found to induce MSC secretion of chemokine (C-C motif) ligand 5 (CCL5) stimulating breast cancer cell metastasis through interaction with the C-C chemokine receptor type 5 (CCR5) receptor [84]. Tumour cell migration towards and entry into the bone marrow metastatic site was shown to be mediated by stromal cell-derived factor 1 (SDF-1α) – a factor secreted by bone marrow MSCs – interaction with the C-X-C chemokine receptor type 4 (CXCR4) receptor expressed on breast and prostate tumour cells [33, 102, 103]