上海交通大学刘军力课题组与上海长海医院王林辉课题组合作发现，邻近脂肪细胞的生热活动促进ccRCC的进展并损害抗肿瘤的疗效。这一研究成果于2021年9月10日在线发表在国际学术期刊《细胞—代谢》上。

研究人员报道了透明细胞肾细胞癌（ccRCC）细胞和肾周脂肪组织（PAT）之间的双向交流。研究人员发现，ccRCC细胞分泌甲状旁腺激素相关蛋白（PTHrP），通过PKA激活促进PAT的棕色化，而PAT介导的产热导致过量乳酸的释放，从而促进ccRCC的生长、侵袭和转移。此外，广泛用于治疗ccRCC的酪氨酸激酶抑制剂（TKI）通过促进PAT的棕色化加强了ccRCC-PAT交流的这种恶性循环。然而，如果通过H89或KT5720对脂肪细胞棕色化进行药物抑制使这种交流短路，那么TKI（舒尼替尼）的抗肿瘤疗效就会增强。

这些结果表明，ccRCC-PAT的交流具有重要临床意义，并且使用联合治疗在提高TKI的疗效方面具有很大的前景。

据悉，透明细胞肾细胞癌（ccRCC）优先侵入肾周脂肪组织（PAT），这一过程与预后不佳有关。然而，这种互动的详细机制仍然难以捉摸。

附：英文原文

Title: The thermogenic activity of adjacent adipocytes fuels the progression of ccRCC and compromises anti-tumor therapeutic efficacy

Author: Gang Wei, Honglin Sun, Kai Dong, Libing Hu, Qi Wang, Qian Zhuang, Yan Zhu, Xianjing Zhang, Yaodi Shao, Huiru Tang, Zhenfei Li, Suzhen Chen, Junxi Lu, Yibing Wang, Xinxin Gan, Tao P. Zhong, Dingkun Gui, Xiaoyong Hu, Linhui Wang, Junli Liu

Issue&Volume: 2021-09-10

Abstract: Clear cell renal cell carcinoma (ccRCC) preferentially invades into perinephric adiposetissue (PAT), a process associated with poor prognosis. However, the detailed mechanismsunderlying this interaction remain elusive. Here, we describe a bi-directional communicationbetween ccRCC cells and the PAT. We found that ccRCC cells secrete parathyroid-hormone-relatedprotein (PTHrP) to promote the browning of PAT by PKA activation, while PAT-mediatedthermogenesis results in the release of excess lactate to enhance ccRCC growth, invasion,and metastasis. Further, tyrosine kinase inhibitors (TKIs) extensively used in thetreatment of ccRCC enhanced this vicious cycle of ccRCC-PAT communication by promotingthe browning of PAT. However, if this cross-communication was short circuited by thepharmacological suppression of adipocyte browning via H89 or KT5720, the anti-tumorefficacy of the TKI, sunitinib, was enhanced. These results suggest that ccRCC-PATcross-communication has important clinical relevance, and use of combined therapyholds great promise in enhancing the efficacy of TKIs.

DOI: 10.1016/j.cmet.2021.08.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00375-2