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与脂肪细胞的相互作用诱导肺腺癌细胞 A549 的迁移和肿瘤生长。

Interaction with adipocytes induces lung adenocarcinoma A549 cell migration and tumor growth.

机构信息

Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1973-1980. doi: 10.3892/mmr.2018.9226. Epub 2018 Jun 26.

Abstract

Adipocytes have been demonstrated to promote the progression of various tumors through modulation of cancer cell metabolism. However, their role in lung cancer progression remains undetermined. In the present study, adipocytes and lung adenocarcinoma A549 cells were cultured in a Transwell co‑culture system. Cancer cells were additionally cultured in conditioned medium, obtained from adipocytes or co‑cultured cells. A MTT and colony formation assay were performed to assess A549 cell proliferation. The expression of epithelial‑mesenchymal transition protein markers E‑cadherin and vimentin were measured by western blotting. A549 cell migration and invasion was determined with wound healing, Transwell and Matrigel assays. Oil Red‑O staining was used to evaluate intracellular lipid content. Colorimetric assays were utilized to detect free fatty acid, glucose uptake, lactate production and triglyceride content in cells. The results revealed a reciprocal interaction between adipocytes and A549 cells, which significantly enhanced A549 cell proliferation and metastasis; whereas, the expression of E‑cadherin was decreased and vimentin was increased in A549 cells. Additionally, A549 cells exhibited metabolic reprogramming in vitro following co‑culture with adipocytes. It was demonstrated that lipid droplets accumulation, glucose consumption and lactate production increased in tumor cells exposed to adipocytes. Furthermore, adipocytes co‑cultured with A549 cells exhibited a decrease in the number and size of lipid droplets, a decrease in the intracellular triglyceride content and a significant increase in the release of free fatty acids. These findings highlighted the crucial role of adipocytes in the modulation of lung adenocarcinoma A549 cell metabolism and suggested the involvement of adipocytes in lung cancer progression.

摘要

脂肪细胞已被证明通过调节癌细胞代谢促进各种肿瘤的进展。然而,它们在肺癌进展中的作用仍未确定。在本研究中,将脂肪细胞和肺腺癌细胞 A549 培养在 Transwell 共培养系统中。将癌细胞另外培养在脂肪细胞或共培养细胞获得的条件培养基中。通过 MTT 和集落形成测定法评估 A549 细胞的增殖。通过 Western blot 测定上皮-间充质转化蛋白标志物 E-钙黏蛋白和波形蛋白的表达。通过划痕愈合、Transwell 和 Matrigel 测定法测定 A549 细胞的迁移和侵袭。用油红-O 染色评估细胞内脂质含量。通过比色法测定细胞中游离脂肪酸、葡萄糖摄取、乳酸生成和甘油三酯含量。结果显示,脂肪细胞和 A549 细胞之间存在相互作用,可显著增强 A549 细胞的增殖和转移;而 A549 细胞中 E-钙黏蛋白的表达降低,波形蛋白的表达增加。此外,与脂肪细胞共培养的 A549 细胞在体外表现出代谢重编程。结果表明,暴露于脂肪细胞的肿瘤细胞中脂质滴积累、葡萄糖消耗和乳酸生成增加。此外,与 A549 细胞共培养的脂肪细胞中脂质滴的数量和大小减少,细胞内甘油三酯含量减少,游离脂肪酸的释放显著增加。这些发现强调了脂肪细胞在调节肺腺癌细胞 A549 细胞代谢中的关键作用,并表明脂肪细胞参与肺癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3772/6072224/d02be9a1bdc0/MMR-18-02-1973-g00.jpg

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