Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
Department of Korean Medicine, Comorbidity Research Institute, College of Korean Medicine, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
J Cell Physiol. 2019 Aug;234(10):18249-18261. doi: 10.1002/jcp.28456. Epub 2019 Mar 9.
Epidemiological evidence suggests that obesity can significantly increase the risk of various cancers, although the mechanisms underlying this link are completely unknown. Here, we analyzed the effect of adipocytes on melanoma and colon cancer cells proliferation, migration, and invasion. The potential effects of conditioned media (CM) obtained from differentiated mouse 3T3-L1 cells and human adipose tissue-derived mesenchymal stem cells (hAMSC) on the proliferation, migration, and invasion of B16BL6 melanoma and colon 26-L5 cancer cells were investigated. The 3T3-L1 and hAMSC CM increased cell proliferation, migration, and invasion in both the cell lines. In addition, adipocytes CM increased matrix metalloproteinase 9 (MMP-9) and MMP-2 activity in both B16BL6 and colon 26-L5 cells. These effects were found to be associated with an increased expression of various oncogenic proteins in B16BL6 and colon 26-L5 cells. Also, adipocyte CM induced Akt and mTOR activation in both tumor cell lines, and the pharmacological inhibition of Akt and mTOR blocked the CM induced Akt as well as mTOR activation and CM-stimulated melanoma and colon cancer cell proliferation, migration, and invasion. These data suggest that adipocyte promotes melanoma and colon cancer progression through modulating the expression of diverse proteins associated with cancer growth and metastasis as well as modulation of the Akt/mTOR signaling.
流行病学证据表明,肥胖显著增加了多种癌症的风险,尽管这种关联的机制尚完全不清楚。在这里,我们分析了脂肪细胞对黑色素瘤和结肠癌细胞增殖、迁移和侵袭的影响。分析了来自分化的小鼠 3T3-L1 细胞和人脂肪组织来源的间充质干细胞(hAMSC)的条件培养基(CM)对 B16BL6 黑色素瘤和结肠 26-L5 癌细胞增殖、迁移和侵袭的潜在影响。3T3-L1 和 hAMSC CM 增加了这两种细胞系中细胞的增殖、迁移和侵袭。此外,脂肪细胞 CM 增加了 B16BL6 和结肠 26-L5 细胞中基质金属蛋白酶 9(MMP-9)和 MMP-2 的活性。这些效应与 B16BL6 和结肠 26-L5 细胞中各种致癌蛋白的表达增加有关。此外,脂肪细胞 CM 在两种肿瘤细胞系中诱导 Akt 和 mTOR 的激活,Akt 和 mTOR 的药理学抑制阻断了 CM 诱导的 Akt 以及 mTOR 激活和 CM 刺激的黑色素瘤和结肠癌细胞的增殖、迁移和侵袭。这些数据表明,脂肪细胞通过调节与癌症生长和转移相关的多种蛋白的表达以及调节 Akt/mTOR 信号通路来促进黑色素瘤和结肠癌细胞的进展。