Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial–mesenchymal transition of the peritoneum

Nakamura, Michihiko; Ono, Yoshihiro; Kanemura, Masanori; Tanaka, Tomohito; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

doi:10.1016/j.ygyno.2015.08.010

Cited by 47 publications

(43 citation statements)

References 27 publications

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“…HGF, secreted by OC cells, has been shown to promote peritoneal implantation and HGF levels are found to be high in OC ascites as compared to benign fluids (219, 220). In addition to promoting OC migration, HGF also induces the migration of peritoneal MC by activating its receptor Met, leading to downstream Akt and ERK1/2 pathway activation.…”

Section: Microenvironmental Regulation Of Emt In Cancers Of the Femalmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

et al. 2017

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Epithelial-to-mesenchymal transition (EMT) is a physiological process that is vital throughout the human lifespan. In addition to contributing to the development of various tissues within the growing embryo, EMT is also responsible for wound healing and tissue regeneration later in adulthood. In this review, we highlight the importance of EMT in the development and normal functioning of the female reproductive organs (the ovaries and the uterus) and describe how dysregulation of EMT can lead to pathological conditions, such as endometriosis, adenomyosis, and carcinogenesis. We also summarize the current literature relating to EMT in the context of ovarian and endometrial carcinomas, with a particular focus on how molecular mechanisms and the tumor microenvironment can govern cancer cell plasticity, therapy resistance, and metastasis.

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Section: Microenvironmental Regulation Of Emt In Cancers Of the Femalmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

et al. 2017

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“…A number of factors in ascites, including CCL18, HGF, LPA and VEGF, have been shown to promote cell migration, invasion and tumorigenesis [20,[26][27][28][29].…”

Section: What Is the Tumor Environment Of Ascitesmentioning

confidence: 99%

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Matte¹,

Bessette²,

Piché³

2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Until recently, ovarian cancer research has mainly focused on the tumor cell themselves ignoring for the most part the surrounding tumor environment. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that major aspects of cancer biology are inluenced by the tumor environment. Malignant ascites accumulates in the peritoneal cavity during ovarian cancer progression and constitutes a unique pro-inlammatory tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. Increasing evidence now supports an active role of ascites in the progression of ovarian cancer. Although much work is still needed to fully understand the contribution of ascites to ovarian cancer aggressiveness, this tumor environment potentially provides a wealth of opportunities for translational research including biomarker discovery and novel therapeutic target identiication. In this review, we discuss recent advances in our understanding of ascites pathophysiology, the characterization of its cellular and acellular contents, the intercellular crosstalks, and how these data can be used to improve the outcome of ovarian cancer.

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“…12, 13, 14, 15 Several in vivo studies have shown that activation of the HGF–cMET signaling pathway triggers cancer invasion and metastasis. 16, 17, 18, 19 Thus, multiple therapeutic agents that target the HGF–cMET pathway in various cancers are under development. For example, several monoclonal antibodies (mAbs) inhibit the HGF–cMET axis by blocking the binding of HGF to cMET or by targeting cMET on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Progress of antibody-based inhibitors of the HGF–cMET axis in cancer therapy

Kim

2017

Exp Mol Med

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Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials. However, to date none of these HGF/cMET inhibitors have shown significant efficacy in clinical trials. Furthermore, no receptor tyrosine kinase inhibitors primarily targeting cMET have been approved. Given that neutralization of HGF or cMET does not cause significant adverse effects, inhibition of the HGF/cMET signaling pathway appears to be safe. In this review, we summarized the completed and ongoing clinical trials testing antibody- or protein-based anticancer drugs targeting cMET and HGF.

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Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial–mesenchymal transition of the peritoneum

Cited by 47 publications

References 27 publications

Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

Progress of antibody-based inhibitors of the HGF–cMET axis in cancer therapy

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