Lipid uptake occurs through caveolae, plasma membrane invaginations formed by caveolins (CAV) and caveolae-associated protein 1 (CAVIN1). Genetic alterations of CAV1N1 and CAV1 modify lipid metabolism and underpin lipodystrophy syndromes. Lipids contribute to tumorigenesis by providing fuel to cancer metabolism and supporting growth and signaling. Tumor stroma promotes tumor proliferation, invasion, and metastasis, but how stromal lipids influence these processes remain to be defined. Here, we show that stromal CAVIN1 regulates lipid abundance in the prostate cancer microenvironment and suppresses metastasis. We show that depletion of CAVIN1 in prostate stromal cells markedly reduces their lipid droplet accumulation and increases inflammation. Stromal cells lacking CAVIN1 enhance prostate cancer cell migration and invasion. Remarkably, they increase lipid uptake and M2 inflammatory macrophage infiltration in the primary tumors and metastasis to distant sites. Our data support the concept that stromal cells contribute to prostate cancer aggressiveness by modulating lipid content and inflammation in the tumor microenvironment. Implications: This study showed that stromal CAVIN1 suppresses prostate cancer metastasis by modulating tumor microenvironment, lipid content, and inflammatory response.

中文翻译：

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基质 CAVIN1 通过调节脂质分布和炎症信号控制前列腺癌微环境和转移

脂质摄取通过小窝、由小窝蛋白 (CAV) 和小窝相关蛋白 1 (CAVIN1) 形成的质膜内陷发生。CAV1N1 和 CAV1 的遗传改变会改变脂质代谢并支持脂肪营养不良综合征。脂质通过为癌症代谢提供燃料并支持生长和信号传导来促进肿瘤发生。肿瘤基质促进肿瘤增殖、侵袭和转移，但基质脂质如何影响这些过程仍有待确定。在这里，我们显示基质 CAVIN1 调节前列腺癌微环境中的脂质丰度并抑制转移。我们表明前列腺基质细胞中 CAVIN1 的消耗显着减少了它们的脂滴积累并增加了炎症。缺乏 CAVIN1 的基质细胞增强了前列腺癌细胞的迁移和侵袭。值得注意的是，它们增加原发性肿瘤中的脂质摄取和 M2 炎性巨噬细胞浸润并转移到远处部位。我们的数据支持这样的概念，即基质细胞通过调节肿瘤微环境中的脂质含量和炎症来促进前列腺癌的侵袭性。启示：这项研究表明，基质 CAVIN1 通过调节肿瘤微环境、脂质含量和炎症反应来抑制前列腺癌转移。