Expression of the miR200 Family of microRNAs in Mesothelial Cells Suppresses the Dissemination of Ovarian Cancer Cells

Sugiyama, Kazuya; Kajiyama, Hiroaki; Shibata, Kiyosumi; Yuan, Hong; Kikkawa, Fumitaka; Senga, Takeshi

doi:10.1158/1535-7163.mct-14-0135

Cited by 29 publications

(32 citation statements)

References 38 publications

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“…Furthermore, the surface of the peritoneum is histologically covered by a single layer of mesothelial cells (MCs), which may have a key function in the development of the tumor microenvironment that supports peritoneal metastasis of OvCa. Moreover, recent studies have shown that activated MCs play an important role in the development of peritoneal metastasis; these studies further demonstrated that MCs increase the adhesive and proliferative properties of OvCa cells. In fact, mesenchymal transition of MCs was reported to be induced by a variety of soluble factors in malignant ascites, and modification of extracellular matrix (ECM) on the mesothelial cells also promoted peritoneal metastasis of OvCa .…”

Section: Introductionmentioning

confidence: 74%

Ovarian cancer‐associated mesothelial cells induce acquired platinum‐resistance in peritoneal metastasis via the FN1/Akt signaling pathway

Yoshihara

Kajiyama

Yokoi

et al. 2020

Intl Journal of Cancer

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Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell‐to‐cell crosstalk or phenotypic alterations including the acquisition of platinum‐resistance in OvCa cells. Herein, we report how OvCa‐associated mesothelial cells (OCAMs) induce platinum‐resistance in OvCa cells through direct cell‐to‐cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF‐β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum‐sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell‐to‐cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF‐β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell‐to‐cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum‐resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination.

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Section: Introductionmentioning

confidence: 74%

Ovarian cancer‐associated mesothelial cells induce acquired platinum‐resistance in peritoneal metastasis via the FN1/Akt signaling pathway

Yoshihara

Kajiyama

Yokoi

et al. 2020

Intl Journal of Cancer

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“…This study was approved by the institutional ethics committee of Nagoya University (approval number: 1234). Stable cell lines that expressed ZsGreen or luciferase were generated using a recombinant retrovirus following a previously described method 51 . In brief, 293 T cells were transfected with the pQCXIP vector encoding each gene as well as with the pVPack-GP and pVPack-Ampho vectors for the production of retrovirus particles (Agilent Technologies, Santa Clara, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Novel Intraperitoneal Treatment With Non-Thermal Plasma-Activated Medium Inhibits Metastatic Potential of Ovarian Cancer Cells

Nakamura

Yang

Utsumi

et al. 2017

Sci Rep

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Non-thermal atmospheric pressure plasma has been proposed as a new therapeutic tool for cancer treatment. Recently, plasma-activated medium (PAM) has been widely studied in various cancer types. However, there are only few reports demonstrating the anti-tumour effects of PAM in an animal model reflecting pathological conditions and the accompanying mechanism. Here we investigated the inhibitory effect of PAM on the metastasis of ovarian cancer ES2 cells in vitro and in vivo. We demonstrated that ES2 cell migration, invasion and adhesion were suppressed by PAM at a certain PAM dilution ratio, whereas cell viability remained unaffected. In an in vivo mouse model of intraperitoneal metastasis, PAM inhibited peritoneal dissemination of ES2 cells, resulting in prolonged survival. Moreover, we assessed the molecular mechanism and found that MMP-9 was decreased by PAM. On further investigation, we also found that PAM prevented the activation of the MAPK pathway by inhibiting the phosphorylation of JNK1/2 and p38 MAPK. These findings indicate that PAM inhibits the metastasis of ovarian cancer cells through reduction of MMP-9 secretion, which is critical for cancer cell motility. Our findings suggest that PAM intraperitoneal therapy may be a promising treatment option for ovarian cancer.

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“…Recently, it was shown that TGF β -stimulated human primary mesothelial cells, which induced expression of MMP-2 and MMP-9, were able to promote cancer cell attachment and proliferation through downregulating members of the miR-200 family. Consequently, the delivery of miR-200 family miRNAs to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination 56 . We recently showed that the direct interaction of OvCa cells with mesothelial cells, which cover the surface of the omentum, causes a DNA methyltransferase 1 (DNMT1) mediated decrease in the expression of miR-193b in the cancer cells 57 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment

et al. 2015

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Cancer cells grow in an environment comprised of multiple components that support tumor growth and contribute to therapy resistance. Major cell types in the tumor micro-environment are fibroblasts, endothelial cells and infiltrating immune cells all of which communicate with cancer cells. One way that these cell types promote cancer progression is by altering expression of miRNAs, small noncoding RNAs that negatively regulate protein expression, either in the cancer cells or in associated normal cells. Changes in miRNA expression can be brought about by direct interaction between the stromal cells and cancer cells, by paracrine factors secreted by any of the cell types, or even through direct communication between cells through secreted miRNAs. Understanding the role of miRNAs in the complex interactions between the tumor and cells in its micro-environment is necessary if we are to understand tumor progression and devise new treatments.

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Expression of the miR200 Family of microRNAs in Mesothelial Cells Suppresses the Dissemination of Ovarian Cancer Cells

Cited by 29 publications

References 38 publications

Ovarian cancer‐associated mesothelial cells induce acquired platinum‐resistance in peritoneal metastasis via the FN1/Akt signaling pathway

Ovarian cancer‐associated mesothelial cells induce acquired platinum‐resistance in peritoneal metastasis via the FN1/Akt signaling pathway

Novel Intraperitoneal Treatment With Non-Thermal Plasma-Activated Medium Inhibits Metastatic Potential of Ovarian Cancer Cells

MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment

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