HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

Sun, Rui; Zhang, Qing; Guo, Ling; Chen, Ming Yuan; Sun, Ying; Cao, Brian; Sun, Jian

doi:10.3892/ol.2012.613

Cited by 9 publications

(9 citation statements)

References 16 publications

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“…Cells harboring different dominant signaling pathways could react differently to HGF. The 97L cell line employed in our study has been reported to express the c-Met receptor [29], which suggests that the HGF/c-Met pathway is most likely the main mechanism through which H-CAFs induce HCC cell proliferation at least in 97L cells. In summary, HGF appears to play a substantial role in the complex mechanisms involved in the proliferative induction of HCC by H-CAFs.…”

Section: Discussionmentioning

confidence: 85%

Cancer-Associated Fibroblasts from Hepatocellular Carcinoma Promote Malignant Cell Proliferation by HGF Secretion

Jia

Wang

Liu³

et al. 2013

PLoS ONE

129

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Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs.

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Section: Discussionmentioning

confidence: 85%

Cancer-Associated Fibroblasts from Hepatocellular Carcinoma Promote Malignant Cell Proliferation by HGF Secretion

Jia

Wang

Liu³

et al. 2013

PLoS ONE

129

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“…FGF members have showed to promote not only fibroblast proliferation but also migration and differentiation through binding to and activating fibroblast growth factor receptors, thereby having its application in tissue regeneration (Yun et al, 2010 ). Besides, HGF and PDGF-BB are important multifunctional growth factors for cell proliferation and mobility (Taniguchi et al, 2004 ; De Donatis et al, 2008 ; Sun et al, 2012 ; Gonzalez et al, 2017 ; Dai et al, 2018 ). However, TGF-β that is reported to regulate fibroblast proliferation through miR-21 modulating PTEN/AKT signaling pathway (Liu et al, 2016 ) or to induce ERK/MAPK signaling pathway to enhance migration of endometrial stromal cells (Liu et al, 2019 ) was not detected in BMMSC- and ADMSC-derived exosomes in this study.…”

Section: Discussionmentioning

confidence: 99%

Differential Wound Healing Capacity of Mesenchymal Stem Cell-Derived Exosomes Originated From Bone Marrow, Adipose Tissue and Umbilical Cord Under Serum- and Xeno-Free Condition

Hoang

Nguyen

et al. 2020

Front. Mol. Biosci.

109

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Exosomes are nano-scale and closed membrane vesicles which are promising for therapeutic applications due to exosome-enclosed therapeutic molecules such as DNA, small RNAs, proteins and lipids. Recently, it has been demonstrated that mesenchymal stem cell (MSC)-derived exosomes have capacity to regulate many biological events associated with wound healing process, such as cell proliferation, cell migration and blood vessel formation. This study investigated the regenerative potentials for cutaneous tissue, in regard to growth factors associated with wound healing and skin cell proliferation and migration, by exosomes released from primary MSCs originated from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) under serum-and xeno-free condition. We found crucial wound healing-mediated growth factors, such as vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), hepatocyte growth factor (HGF), and platelet-derived growth factor BB (PDGF-BB) in exosomes derived from all three MSC sources. However, expression levels of these growth factors in exosomes were influenced by MSC origins, especially transforming growth factor beta (TGF-β) was only detected in UCMSC-derived exosomes. All exosomes released by three MSCs sources induced keratinocyte and fibroblast proliferation and migration; and, the induction of cell migration is a dependent manner with the higher dose of exosomes was used (20 µg), the faster migration rate was observed. Additionally, the influences of exosomes on cell proliferation and migration was associated with exosome origins and also target cells of exosomes that the greatest induction of primary dermal fibroblasts belongs to BMMSC-derived exosomes Hoang et al. Mesenchymal Stem Cell-Derived Exosomes and keratinocytes belongs to UCMSC-derived exosomes. Data from this study indicated that BMMSCs and UCMSCs under clinical condition secreted exosomes are promising to develop into therapeutic products for wound healing treatment.

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“…HGF has been shown to promote cell migration and invasion [42], [65], [66] and is required in cell migration assays. The EGFR inhibitors were ineffective in blocking cell migration in all of the cell lines (A549, H1975 and H1650) except for EGFR wildtype cell line H292 which was sensitive to EGFR inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Lung Tumor Microenvironment Modulates Therapeutic Compound Responsiveness In Vitro – Implication for Drug Development

Ekert

Johnson

Strake³

et al. 2014

PLoS ONE

138

140

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Three-dimensional (3D) cell culture is gaining acceptance in response to the need for cellular models that better mimic physiologic tissues. Spheroids are one such 3D model where clusters of cells will undergo self-assembly to form viable, 3D tumor-like structures. However, to date little is known about how spheroid biology compares to that of the more traditional and widely utilized 2D monolayer cultures. Therefore, the goal of this study was to characterize the phenotypic and functional differences between lung tumor cells grown as 2D monolayer cultures, versus cells grown as 3D spheroids. Eight lung tumor cell lines, displaying varying levels of epidermal growth factor receptor (EGFR) and cMET protein expression, were used to develop a 3D spheroid cell culture model using low attachment U-bottom plates. The 3D spheroids were compared with cells grown in monolayer for 1) EGFR and cMET receptor expression, as determined by flow cytometry, 2) EGFR and cMET phosphorylation by MSD assay, and 3) cell proliferation in response to epidermal growth factor (EGF) and hepatocyte growth factor (HGF). In addition, drug responsiveness to EGFR and cMET inhibitors (Erlotinib, Crizotinib, Cetuximab [Erbitux] and Onartuzumab [MetMab]) was evaluated by measuring the extent of cell proliferation and migration. Data showed that EGFR and cMET expression is reduced at day four of untreated spheroid culture compared to monolayer. Basal phosphorylation of EGFR and cMET was higher in spheroids compared to monolayer cultures. Spheroids showed reduced EGFR and cMET phosphorylation when stimulated with ligand compared to 2D cultures. Spheroids showed an altered cell proliferation response to HGF, as well as to EGFR and cMET inhibitors, compared to monolayer cultures. Finally, spheroid cultures showed exceptional utility in a cell migration assay. Overall, the 3D spheroid culture changed the cellular response to drugs and growth factors and may more accurately mimic the natural tumor microenvironment.

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HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

Cited by 9 publications

References 16 publications

Cancer-Associated Fibroblasts from Hepatocellular Carcinoma Promote Malignant Cell Proliferation by HGF Secretion

Cancer-Associated Fibroblasts from Hepatocellular Carcinoma Promote Malignant Cell Proliferation by HGF Secretion

Differential Wound Healing Capacity of Mesenchymal Stem Cell-Derived Exosomes Originated From Bone Marrow, Adipose Tissue and Umbilical Cord Under Serum- and Xeno-Free Condition

Three-Dimensional Lung Tumor Microenvironment Modulates Therapeutic Compound Responsiveness In Vitro – Implication for Drug Development

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