Amemori Sadahiro, Ootani Akifumi, Aoki Shigehisa, Fujise Takehiro, Shimoda Ryo, Kakimoto Takashi, Shiraishi Ryosuke, Sakata Yasuhisa, Tsunada Seji, Iwakiri Ryuichi, Fujimoto Kazuma
Department of Internal Medicine, Saga Medical School, Saga, Japan.
Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G923-9. doi: 10.1152/ajpgi.00145.2006.
Obesity, a risk factor for colon cancer, is associated with elevated serum levels of leptin, a protein produced by adipocytes. The aim of the present study was to clarify the effects of adipose tissue on colon cancer proliferation by using cultured cell lines. To achieve this, colon cancer cells (CACO-2, T84, and HT29) were cocultured with adipose tissue, isolated mature adipocytes, and isolated preadipocytes in a three-dimensional collagen gel culture system. The adipocytes and preadipocytes used were isolated from C57BL/6J and leptin-deficient ob/ob mice. Proliferation of the cancer cells was evaluated by nuclear bromodeoxyuridine uptake. The adipose tissue, mature adipocytes, and preadipocytes isolated from C57BL/6J mice significantly increased the proliferation of the colon cancer cells. This trophic effect of mature adipocytes on the cancer cell lines was observed only for cells from lean littermates and not for those from ob/ob mice. In contrast, the trophic effect of preadipocytes was not abolished in ob/ob mice, and this finding was supported by the result that leptin had a trophic effect on cancer cells. In conclusion, adipocytes were able to enhance the proliferation of colon cancer cells in vitro, partly via leptin, suggesting that adipose tissues, including mature adipocytes and preadipocytes, may promote the growth of colorectal cancer.
肥胖是结肠癌的一个风险因素,与血清中瘦素水平升高有关,瘦素是一种由脂肪细胞产生的蛋白质。本研究的目的是通过使用培养的细胞系来阐明脂肪组织对结肠癌细胞增殖的影响。为实现这一目的,在三维胶原凝胶培养系统中,将结肠癌细胞(CACO - 2、T84和HT29)与脂肪组织、分离的成熟脂肪细胞和分离的前脂肪细胞共同培养。所用的脂肪细胞和前脂肪细胞是从C57BL/6J小鼠和瘦素缺陷型ob/ob小鼠中分离得到的。通过细胞核溴脱氧尿苷摄取来评估癌细胞的增殖。从C57BL/6J小鼠分离的脂肪组织、成熟脂肪细胞和前脂肪细胞显著增加了结肠癌细胞的增殖。成熟脂肪细胞对癌细胞系的这种营养作用仅在来自瘦小鼠同窝仔的细胞中观察到,而在来自ob/ob小鼠的细胞中未观察到。相反,前脂肪细胞的营养作用在ob/ob小鼠中并未消除,瘦素对癌细胞具有营养作用这一结果支持了这一发现。总之,脂肪细胞能够在体外增强结肠癌细胞的增殖,部分是通过瘦素实现的,这表明包括成熟脂肪细胞和前脂肪细胞在内的脂肪组织可能促进结直肠癌的生长。