title: Subcutaneous adipocytes promote melanoma cell growth by activating the Akt signaling pathway: role of palmitic acid.
abstract: Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and. Electronic address: hykwan@hkbu.edu.hk.
authors.forename: Hiu Yee
authors.initials: HY
authors.lastname: Kwan
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, and the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chao
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Chi Leung
authors.initials: CL
authors.lastname: Chan
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Huihui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Anfernee Kai Wing
authors.initials: AKW
authors.lastname: Tse
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and.
authors.forename: Wang Fun
authors.initials: WF
authors.lastname: Fong
authors.affiliation: Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China and. Electronic address: zlyu@hkbu.edu.hk.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
mesh_terms: D052438:Adipocytes, White / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D004789:Enzyme Activation; D050356:Lipid Metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D050151:Subcutaneous Fat / Q000473:pathology; D047368:Tumor Burden
chemical_list: D019308:Palmitic Acid; D051057:Proto-Oncogene Proteins c-akt
keywords: Adipocyte; Akt PKB; Cancer; Fatty acid; Obesity