Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Cell Commun Signal. 2018 Jun 18;16(1):32. doi: 10.1186/s12964-018-0221-6.
To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells.
A Transwell co-culture system was used in which human breast cancer cells were cultured in the absence or presence of differentiated murine 3 T3-L1 adipocytes. Migration/invasion and proliferation abilities were compared between breast cancer cells that were cultivated alone and those co-cultivated with mature adipocytes. The ability of lipolysis in breast cancer cells were measured, as well as the expression of the rate-limiting lipase ATGL and fatty acid transporter FABP5. ATGL and FABP5 were then ablated to investigate their impact on the aggressiveness of breast cancer cells that were surrounded by adipocytes. Further, immunohistochemistry was performed to detect differential expression of ATGL and FABP5 in breast cancer tissue sections.
The migration and invasion abilities of cancer cells were significantly enhanced after co-culture with adipocytes, accompanied by elevated lipolysis and expression of ATGL and FABP5. Abrogation of ATGL and FABP5 sharply attenuated the malignancy of co-cultivated breast cancer cells. However, this phenomenon was not observed if a lipid emulsion was added to the culture medium to substitute for adipocytes. Furthermore, epithelial-mesenchymal transaction was induced in co-cultivated breast cancer cells. That may partially due to the stimulation of PPARβ/δ and MAPK, which was resulted from upregulation of FABP5. As evidenced by immunohistochemistry, ATGL and FABP5 also had higher expression levels at the invasive front of the breast tumor, in where the adipocytes abound, compared to the central area in tissue specimens.
Lipid originating from tumor-surrounding adipocytes could be transferred into breast cancer cells. Adipocyte-cancer cell crosstalk rather than lipids alone induced upregulation of lipases and fatty acid transport protein in cancer cells to utilize stored lipids for tumor progression. The increased expression of the key lipase ATGL and intracellular fatty acid trafficking protein FABP5 played crucial roles in this process via fueling or signaling.
为了确定脂肪细胞衍生的脂质是否可以转移到乳腺癌细胞中，并研究乳腺癌细胞中随后的脂解和脂肪酸转运的潜在机制。
使用 Transwell 共培养系统，将人乳腺癌细胞在存在或不存在分化的小鼠 3T3-L1 脂肪细胞的情况下进行培养。比较单独培养的乳腺癌细胞和与成熟脂肪细胞共培养的乳腺癌细胞的迁移/侵袭和增殖能力。测量乳腺癌细胞的脂解能力，以及限速脂肪酶 ATGL 和脂肪酸转运蛋白 FABP5 的表达。然后敲除 ATGL 和 FABP5，以研究它们对被脂肪细胞包围的乳腺癌细胞侵袭性的影响。此外，进行免疫组织化学检测以检测 ATGL 和 FABP5 在乳腺癌组织切片中的差异表达。
与脂肪细胞共培养后，癌细胞的迁移和侵袭能力显著增强，伴随着脂解和 ATGL 和 FABP5 的表达升高。敲除 ATGL 和 FABP5 可显著减弱共培养乳腺癌细胞的恶性程度。然而，如果在培养基中添加脂肪乳液代替脂肪细胞，则不会观察到这种现象。此外，共培养的乳腺癌细胞中发生上皮-间充质转化。这可能部分归因于 FABP5 的上调导致 PPARβ/δ 和 MAPK 的激活。免疫组织化学结果表明，与组织标本的中心区域相比，在富含脂肪细胞的乳腺癌肿瘤侵袭前沿处，ATGL 和 FABP5 的表达水平也更高。
源自肿瘤周围脂肪细胞的脂质可以转移到乳腺癌细胞中。脂肪细胞与癌细胞的相互作用而不仅仅是脂质本身，会诱导癌细胞中脂肪酶和脂肪酸转运蛋白的上调，以利用储存的脂质促进肿瘤进展。关键脂肪酶 ATGL 和细胞内脂肪酸转运蛋白 FABP5 的表达增加在这个过程中发挥了重要作用，为肿瘤提供燃料或信号。
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