Abstract
Mesenchymal stem cells (MSCs) have both stemness and multi-modulatory activities on other cells, and the immunosuppressive and tumor-promotive mechanisms have been intensively investigated in cancer. The role of MSCs appears to be revealed in tumor aggravation, and targeting MSCs seems to be a promising strategy for treating cancer patients. However, it is still impractical in clinical therapy, since the precise MSCs are poorly understood in the in vivo setting. In previous studies, MSCs were obtained from different sources, and were prepared by ex vivo expansion for a long term. The inconsistent experimental conditions made the in vivo MSCs obscure. To define the MSCs in the host is a priority issue for targeting MSCs in cancer therapy. We recently identified a unique subpopulation of MSCs increasing in mice and human with cancer metastasis. These MSCs are specifically expanded by metastatic tumor cells, and promote tumor progression and dissemination accompanied by immune suppression and dysfunction in the host, more powerfully than normal MSCs growing without interference of cancer. In this review, we summarize current knowledge of the role of MSCs in tumor aggravation, along with our new findings of the bizarre MSCs.
Highlights
Mesenchymal stem cells (MSCs) have stemness including self-renewability and pluripotency to differentiate into adipocytes, osteocytes, chondrocytes, fibroblasts, pericytes and more, and have multiple immunoregulatory properties for maintaining immune tolerance (Uccelli et al, 2008; Liu et al, 2009)
Using murine and human tumor cells with typical features of epithelialto-mesenchymal transition (EMT), high motility and invasivity, following transduction of a cDNA coding for snail family zinc finger 1 (Snail), we found that Snail+ metastatic tumor cells release a large amount of TSP1 (Kudo-Saito et al, 2009), CCL2 (Kudo-Saito et al, 2013b), and FSTL1 (Kudo-Saito, 2013; KudoSaito et al, 2013a), all of which can generate immune suppression and dysfunction mediated by immunoregulatory cells including CD4+Foxp3+ Tregs, CD11c+MHC IIlow/− DCregs and CD45−ALCAM+ MSCs, and functionally impaired CD8low T cells
In another study focusing on human endogenous retrovirus antigen H (HERV-H) that is frequently and highly expressed in metastatic tumor cells, we found that CD45−CD271+ MSCs are recruited by CCL19 released from HERVH+ tumor cells in the microenvironment (Kudo-Saito et al, 2014)
Summary
Mesenchymal stem cells (MSCs) have stemness including self-renewability and pluripotency to differentiate into adipocytes, osteocytes, chondrocytes, fibroblasts, pericytes and more, and have multiple immunoregulatory properties for maintaining immune tolerance (Uccelli et al, 2008; Liu et al, 2009). Using murine and human tumor cells with typical features of EMT, high motility and invasivity, following transduction of a cDNA coding for snail family zinc finger 1 (Snail), we found that Snail+ metastatic tumor cells release a large amount of TSP1 (Kudo-Saito et al, 2009), CCL2 (Kudo-Saito et al, 2013b), and FSTL1 (Kudo-Saito, 2013; KudoSaito et al, 2013a), all of which can generate immune suppression and dysfunction mediated by immunoregulatory cells including CD4+Foxp3+ Tregs, CD11c+MHC IIlow/− DCregs and CD45−ALCAM+ MSCs, and functionally impaired CD8low T cells This pathway totally accelerates cancer metastasis in the host. We summarize the current knowledge of the diversified functional role of the bizarre sMSCs (Figure 1) including normal MSCs in tumor aggravation
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