Adiponectin induces CXCL1 secretion from cancer cells and promotes tumor angiogenesis by inducing stromal fibroblast senescence.
Adiponectin is an adipocyte-specific adipocytokine with proliferative and pro-angiogenic effects that regulates many biological processes, including immunity, insulin resistance, and inflammation. The oncogenic role of adiponectin has been implicated in several cancer types. Stromal cells within tumor contribute tumor growth and angiogenesis; however, it is not clear that how adiponectin regulates stromal cell-mediated tumorigenesis. In this study, using the tumor xenograft models, we demonstrated that tumor development was severely impaired in mouse subcutaneous cancer tissue and metastasis tumor tissue in adiponectin knockout mice. Our results indicated adiponectin deficiency resulted in decrease of blood vessel and stromal senescent fibroblasts in subcutaneous and metastasis tumor tissue. These observations were confirmed in vitro, in which co-cultured tumor cells and fibroblasts treated with adiponectin promoted ECs tube formation. A secretion of CXCL1 by adiponectin-treated tumor cells was observed during the process of inducing stromal fibroblast senescence. Furthermore, stromal cells senescence was through p53 and p16 pathways. Taken together, our results indicate that adiponectin promotes stromal cell senescence within invasive colon cancer contributing to angiogenesis and tumor growth in part through the production of CXCL1 and may serve as a therapeutic target for tumor patients. © 2015 Wiley Periodicals, Inc.
The Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China.
Lun
L
Cai
The Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China.
Shengyuan
S
Xu
The Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China.
Chunmei
C
Piao
The Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China.
Shulan
S
Qiu
Department of Pathology, Capital Medical University, Beijing, China.
Huihua
H
Li
The Key Laboratory of Remodeling-Related Cardiovascular Diseases Ministry of Education, Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, Beijing, China. jdu@bcm.edu.
Jie
J
Du
D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000473:pathology
C499918:ADIPOQ protein, human; D052242:Adiponectin; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1
CXCL1; adiponectin; senescence; stromal cells; tumor angiogenesis