Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells

Nishimura, Koshi; Semba, Shuho; Aoyagi, Kazuhiko; Sasaki, Hiroki; Yokozaki, Hiroshi

doi:10.1159/000337296

Cited by 82 publications

(60 citation statements)

References 108 publications

(62 reference statements)

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“…Salinomycin, a selective breast cancer stem cell inhibitor, has been reported to decrease stem cell-related genes such as CCND1 (cyclin D1), LEF1 and FN1, which are targets of Wnt signaling (17). The role of Wnt signaling in different cell types may be an interesting target for cancer stem cell machinery (18,19). Gene expression was analyzed to investigate whether these stem cell-related genes were involved in the cellular phenotypic changes.…”

Section: Comparing the Expression Of Emt-related Genes In Mscs And DImentioning

confidence: 99%

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

Tanabe

Aoyagi²,

Yokozaki

et al. 2014

International Journal of Oncology

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Abstract. Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer (GC) compared with intestinal-type GC; however, histological typing is currently the only method for distinguishing these two major types of GC. We compared the gene expression profiles of 12 bone marrow-derived mesenchymal stem cell cultures and 5 diffuse-type GC tissue samples. Numerous upregulated or downregulated genes were identified in diffuse-type GC, including CDH1, CDH2, VIM, WNT4 and WNT5. Among these genes, the mRNA ratio of CDH2 to CDH1 could distinguish the 15 diffuse-type GC samples from the 17 intestinal-type GC samples. Our results suggested that the mesenchymal features were more prominent in diffuse-type GC than in intestinal-type GC, but were weaker in diffuse-type GC than in mesenchymal stem cells. Diffuse-type GC that has undergone extensive EMT, which has a poor prognosis, can be identified by quantitative PCR analysis of only two genes.

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Section: Comparing the Expression Of Emt-related Genes In Mscs And DImentioning

confidence: 99%

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

Tanabe

Aoyagi²,

Yokozaki

et al. 2014

International Journal of Oncology

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“…In an experimental model of coculturing of human GC-derived MKN-7 cells and bone marrow-derived CAFs, their direct interaction increased WNT5A and transforming growth factor (TGF)-β expression in GC cells and CAFs, respectively [3]. WNT5A is a member of the WNT family of secreted growth factors, which are 38-45 kDa rich with cysteine and hydrophobic signal peptides and play crucial roles in various developmental processes and tissue homeostasis in adults [4,5].…”

Section: Introductionmentioning

confidence: 99%

WNT5A is a Key Regulator of the Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties in Human Gastric Carcinoma Cells

Kanzawa¹,

Semba²,

Hara

et al. 2013

Pathobiology

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Objective: Direct interaction with cancer-associated fibroblasts triggers WNT5A expression in human gastric carcinoma (GC) cells. In this study, we performed gene transduction experiments to investigate the significance of WNT5A in the GC tumor microenvironment. Methods: Gene transduction (pWNT5A and shWNT5A) was performed in human GC-derived MKN-7 cells. Altered gene expression was examined by RT-PCR and cDNA microarray analysis. Immunohistochemical examination was carried out in human GC tissues. Results: Transduction of exogenous WNT5A expression into MKN-7 cells upregulated genes related to the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), and the pWNT5A transfectant showed high tumorigenicity in vivo. These results were confirmed by knockdown experiments using a lentivirus expressing shWNT5A. A cDNA microarray analysis suggested that depletion of endogenous WNT5A downregulated genes involved in intracellular signaling, chemokine-cytokine interaction and focal adhesion. High levels of WNT5A expression were observed in 66% of GC cases, with significant correlation with histological type. Interestingly, in intestinal-type GCs, WNT5A expression was detected in the periphery of tumor nests. Conclusions: WNT5A regulates the induction of EMT and the maintenance of CSC properties in MKN-7 cells. WNT5A may play an important role in constructing an advantageous tumor microenvironment for the progression and development of human GC.

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“…This suggests that there may be a direct link between EMT and the acquirement of CTC properties as well as additional dedifferentiation to having CSC properties. It would thus follow that MSCs contribute to a microenvironment that specifically supports circulating CSCs [41], which are able to metastasize and form new metastatic nodules in distant sites [42]. Besides miR-10b, other microRNAs of note include miR-373 and miR-155.…”

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confidence: 99%

Involvement of Mesenchymal Stem Cells in Cancer Progression and Metastases

Chang¹,

Schwertschkow²,

Nolta³

et al. 2015

CCDT

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Mesenchymal stem/stromal cells (MSCs) are known to be the helpers for the healing of tissue damage, often referred to as ambulatory cells. However, MSCs are also recruited by cancer cells to similarly aid in tumor growth and progression. In this review, some of the key steps in cancer progression and metastases are described including the various steps in which MSCs participate and may play important roles. MSCs aid in cancer cells' ability to evade immune attack, while promoting tumor angiogenesis, even being counter-acting against chemotherapeutics and other drugs used to fight various cancers. Furthermore, MSCs participate in many of the crucial steps in invasion and metastasis, including stimulating the epithelial-mesenchymal transition (EMT) and induction of stem-like properties that allow cancer stem cells to increase their survivability through the circulation. These steps are described in detail. Differences between circulating tumor cells (CTCs) and cancer stem cells (CSCs) are discussed, along with descriptions of the formation of a pre-metastatic niche, the role of exosomes from both cancer cells and MSCs in metastasis and tumor reseeding (self-seeding). More and more, MSCs are being proposed as a promising tumor targeting drug-delivery tool. In order to fulfill this promise, further understanding of the precise roles that MSCs play in the process of cancer metastases must be achieved, in attempting to create remedies that will improve the outcome of available therapeutics.

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Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells

Cited by 82 publications

References 108 publications

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

WNT5A is a Key Regulator of the Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties in Human Gastric Carcinoma Cells

Involvement of Mesenchymal Stem Cells in Cancer Progression and Metastases

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