Amphiregulin enhances VEGF-A production in human chondrosarcoma cells and promotes angiogenesis by inhibiting miR-206 via FAK/c-Src/PKCδ pathway.
Chondrosarcoma is the second most common primary malignancy of bone after myeloma and osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). The expression of VEGF-A has been recognized as a prognostic marker in angiogenesis. Amphiregulin (AR), an epidermal growth factor receptor ligand, promotes tumor proliferation, metastasis and angiogenesis. However, the role of AR in VEGF-A expression and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that AR promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, AR-enhanced VEGF-A expression and angiogenesis involved the FAK, c-Src and PKCδ signaling pathways, while miR-206 expression was negatively mediated by AR via the FAK, c-Src and PKCδ pathways. Our results illustrate the clinical significance between AR, VEGF-A and miR-206, as well as tumor stage, in human chondrosarcoma. AR may represent a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma.
Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.
Chao-Qun
CQ
Wang
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Yu-Wen
YW
Huang
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
Shih-Wei
SW
Wang
Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
Yuan-Li
YL
Huang
School of Medicine, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Chun-Hao
CH
Tsai
Department of Surgical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.
Yong-Ming
YM
Zhao
Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.
Bi-Fei
BF
Huang
Department of Orthopedics, Dongyang People's Hospital, Wenzhou Medical University, Dongyang, China.
Guo-Hong
GH
Xu
Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin County, Taiwan.
Yi-Chin
YC
Fong
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: chtang@mail.cmu.edu.tw.
Chih-Hsin
CH
Tang
D066258:Amphiregulin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002813:Chondrosarcoma / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049033:Chorioallantoic Membrane / Q000098:blood supply; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000201:enzymology / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
C587848:AREG protein, human; D066258:Amphiregulin; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta
Amphiregulin; Angiogenesis; VEGF-A; miR-206