Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milano, Italy.
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford OX3 0BP, UK.
Cells. 2022 Aug 3;11(15):2388. doi: 10.3390/cells11152388.
In recent decades, obesity has widely emerged as an important risk factor for prostate cancer (PCa). Adipose tissue and PCa cells have been shown to orchestrate a complex interaction network to support tumor growth and evolution; nonetheless, the study of this communication has only been focused on soluble factors, although increasing evidence highlights the key role of extracellular vesicles (EVs) in the modulation of tumor progression.
In the present study, we found that EVs derived from 3T3-L1 adipocytes could affect PC3 and DU145 PCa cell traits, inducing increased proliferation, migration and invasion. Furthermore, conditioning of both PCa cell lines with adipocyte-released EVs resulted in lower sensitivity to docetaxel, with reduced phosphatidylserine externalization and decreased caspase 3 and PARP cleavage. In particular, these alterations were paralleled by an Akt/HIF-1α axis-related Warburg effect, characterized by enhanced glucose consumption, lactate release and ATP production.
Collectively, these findings demonstrate that EV-mediated crosstalk exists between adipocytes and PCa, driving tumor aggressiveness.
近几十年来，肥胖已广泛成为前列腺癌（PCa）的一个重要危险因素。脂肪组织和 PCa 细胞已被证明能协调一个复杂的相互作用网络，以支持肿瘤的生长和演进；尽管如此，对这种交流的研究仅集中在可溶性因子上，尽管越来越多的证据强调了细胞外囊泡（EVs）在调节肿瘤进展方面的关键作用。
在本研究中，我们发现，源自 3T3-L1 脂肪细胞的 EVs 可影响 PC3 和 DU145 PCa 细胞的特性，诱导增殖、迁移和侵袭增加。此外，用脂肪细胞释放的 EVs 对两种 PCa 细胞系进行条件处理，导致对多西紫杉醇的敏感性降低，同时细胞外膜磷酯酰丝氨酸（phosphatidylserine）的外排减少，caspase 3 和 PARP 裂解减少。特别是，这些改变与 Akt/HIF-1α 轴相关的瓦博格效应平行，其特征是葡萄糖消耗、乳酸释放和 ATP 产生增加。
总的来说，这些发现表明，脂肪细胞与 PCa 之间存在 EV 介导的串扰，从而推动肿瘤的侵袭性。
