Amphiregulin enhances VEGF-A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR-206 via FAK/c-Src/PKCδ pathway

Wang, Chaoqun; Huang, Yu-Wen; Wang, Shih‐Wei; Huang, Yuan‐Li; Tsai, Chun‐Hao; Zhao, Yongming; Huang, Bifei; Xu, Guiyun; Fong, Yi‐Chin; Tang, Chih‐Hsin

doi:10.1016/j.canlet.2016.10.010

Cited by 54 publications

(51 citation statements)

References 38 publications

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“…These facts may account for tumour relapses during anti‐VEGF‐A therapy and suggest the heterogeneity of the biological action of VEGF‐A in carcinogenesis. Importantly, VEGF‐A production is also under the control of EGFR ligands, as has been reported for AREG in human chondrosarcoma cells . Notably, AREG was also up‐regulated in our A platensis ‐treated pancreatic cancer cells.…”

Section: Discussionsupporting

confidence: 79%

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Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer

Markova

Koníčková

Vaňková

et al. 2020

J Cellular Molecular Medi

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Arthrospira platensis, a blue‐green alga, is a popular nutraceutical substance having potent antioxidant properties with potential anti‐carcinogenic activities. The aim of our study was to assess the possible anti‐angiogenic effects of A platensis in an experimental model of pancreatic cancer. The effects of an A platensis extract were investigated on human pancreatic cancer cells (PA‐TU‐8902) and immortalized endothelial‐like cells (Ea.hy926). PA‐TU‐8902 pancreatic tumours xenografted to athymic mice were also examined. In vitro migration and invasiveness assays were performed on the tested cells. Multiple angiogenic factors and signalling pathways were analysed in the epithelial, endothelial and cancer cells, and tumour tissue. The A platensis extract exerted inhibitory effects on both migration and invasion of pancreatic cancer as well as endothelial‐like cells. Tumours of mice treated with A platensis exhibited much lesser degrees of vascularization as measured by CD31 immunostaining (P = .004). Surprisingly, the VEGF‐A mRNA and protein expressions were up‐regulated in pancreatic cancer cells. A platensis inhibited ERK activation upstream of Raf and suppressed the expression of ERK‐regulated proteins. Treatment of pancreatic cancer with A platensis was associated with suppressive effects on migration and invasiveness with various anti‐angiogenic features, which might account for the anticancer effects of this blue‐green alga.

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Section: Discussionsupporting

confidence: 79%

“…Importantly, VEGF-A production is also under the control of EGFR ligands, as has been reported for AREG in human chondrosarcoma cells. 45 Notably, AREG was also up-regulated in our A platensis-treated pancreatic cancer cells.…”

Section: Our Results On the Increased Production Of Vegf-a Induced Bymentioning

confidence: 68%

Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer

Markova

Koníčková

Vaňková

et al. 2020

J Cellular Molecular Medi

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“…4A). Moreover, c-Src has been implicated in the downstream signalling of FAK activation (Lin et al, 2013;Wang et al, 2017). In this study, VEGF increased c-Src phosphorylation, which was antagonized by glucocerebroside ( Figure 4B).…”

Section: Glucocerebroside Reduces Vegf-induced Fak and C-src Activationsupporting

confidence: 49%

Glucocerebroside reduces endothelial progenitor cell-induced angiogenesis

Lee

Wang

et al. 2019

Food and Agricultural Immunology

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The recruitment of bone marrow-derived endothelial progenitor cells (EPCs) facilitates physiological and pathological processes involved in new blood vessel synthesis. Glucocerebroside, an extract of Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration, although its anti-angiogenic properties in human EPCs has remained largely unknown up until now. We describe how glucocerebroside reduces migration as well as tube formation induced by vascular endothelial growth factor (VEGF) stimulation in human EPCs, without affecting cell viability. This inhibitory effect was achieved through the focal adhesion kinase (FAK)/c-Src pathways. We also found that glucocerebroside reduced VEGFpromoted upregulation of the transcription factor Runx2 in the EPCs. The in vivo chick embryo chorioallantoic membrane model demonstrated that glucocerebroside reduces new vessel formation. Our investigation is the first to show that glucocerebroside reduces angiogenesis in human EPCs and to describe the underlying mechanisms. Further investigations are needed to examine the effects of glucocerebroside in other angiogenesis-related disorders. ARTICLE HISTORY

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“…48 A similar effect has been found in chondrosarcoma, where AR can increase integrin expression and thereby promote cell | 1821 migration. 33 More recently, research demonstrated that AR enhances the production of VEGF-A in human chondrosarcoma cells and thereby promotes angiogenesis 34 . Bone metastasis is the most frequent complication in non-small cell lung cancer (NSCLC).…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23][24][25][26] AR is also implicated in the regulation of migration, invasion, and drug resistance in cancer cells. [27][28][29][30][31][32] In regard to chondrosarcoma, it has been reported that AR can promote cell migration 33 and angiogenesis 34 ; however, the role of AR in drug resistance is still largely unknown.…”

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confidence: 99%

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

Chen

Huang

Lee

et al. 2018

Molecular Carcinogenesis

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Chondrosarcoma is characterized by the ability to produce extracellular matrix of cartilage. Curative surgical resection becomes difficult when high-grade chondrosarcoma metastasizes to other parts of the body. Doxorubicin (Dox) has been widely used clinically to treat many different types of cancers, including chondrosarcomas. However, chondrosarcoma is often resistant to chemotherapy and radiotherapy. New systemic treatment regimens are needed to improve the prognosis. Amphiregulin (AR) has been reported to be involved in cancer metastasis and drug resistance. The aim of the present study was to investigate the role of AR on cell migration and Dox sensitivity. To gain insight into the mechanisms used by AR to mediate its effects, we generated two chondrosarcoma cell lines, migration-prone JJ012 and Dox-resistant SW1353, to analyze the relationship between AR levels and cell functions. AR was highly expressed and secreted in mobile and drug-resistant cells. Next, we used the lentivirus-mediated RNAi system to knock down AR expression and found that AR silencing was significantly attenuated in cell migration and drug resistance. In addition, we used exogenous recombinant AR (r-AR) to confirm cell function and we introduced antibody array analysis to investigate pathways of AR activation. The results showed that AR can promote migratory activity and Dox resistance through activation of the MAPK pathway. Whereas the inhibition of the MAPK pathway has the potential to inhibit chondrosarcoma cell migration, p38 inhibition, and ERK activation may render cells more sensitive to Dox. These findings suggest that combining AR with MAPK blockade may effectively treat chondrosarcoma.

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Amphiregulin enhances VEGF-A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR-206 via FAK/c-Src/PKCδ pathway

Cited by 54 publications

References 38 publications

Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer

Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer

Glucocerebroside reduces endothelial progenitor cell-induced angiogenesis

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

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