Oregel-Cortez Mario Israel, Frayde-Gómez Héctor, Quintana-González Georgina, García-González Victor, Vazquez-Jimenez Jose Gustavo, Galindo-Hernández Octavio
Departamento de Bioquimíca, Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali 21100, Baja California, Mexico.
Laboratorio Multidisciplinario de Estudios Metabólicos y Cáncer, Universidad Autónoma de Baja California, Mexicali 21100, Baja California, Mexico.
Life (Basel). 2023 Dec 10;13(12):2321. doi: 10.3390/life13122321.
Resistin is an adipokine with metabolic and inflammatory functions. Epidemiological and translational studies report that an increase in plasma levels and tissue expression of resistin increases the aggressiveness of prostate tumor cells. Extracellular vesicles (EVs) are secreted constitutively and induced by cytokines, growth factors, and calcium and are found in multiple biological fluids such as saliva, serum, semen, and urine. In particular, EVs have been shown to promote tumor progression through the induction of proliferation, growth, angiogenesis, resistance to chemotherapy, and metastasis. However, the role of resistin in the migration, invasion, and secretion of EVs in invasive prostate tumor cells remains to be studied. In the present study, we demonstrate that resistin induces increased migration and invasion in PC3 cells. In addition, these phenomena are accompanied by increased p-FAK levels and increased secretion of MMP-2 and MMP-9 in resistin-treated PC3 cells. Interestingly, EVs isolated from supernatants of PC3 cells treated with resistin induce an increase in migration and invasion accompanied by high MMP-2 and MMP-9 secretion in an autocrine stimulation model. In summary, our data for the first time demonstrate that resistin induces migration and invasion, partly through the secretion of EVs with pro-invasive characteristics in PC3 cells.
抵抗素是一种具有代谢和炎症功能的脂肪因子。流行病学和转化研究报告称，血浆中抵抗素水平升高以及组织中抵抗素表达增加会增强前列腺肿瘤细胞的侵袭性。细胞外囊泡（EVs）是由细胞因子、生长因子和钙诱导并持续分泌的，存在于多种生物体液中，如唾液、血清、精液和尿液。特别是，EVs已被证明可通过诱导增殖、生长、血管生成、化疗耐药性和转移来促进肿瘤进展。然而，抵抗素在侵袭性前列腺肿瘤细胞的迁移、侵袭以及EVs分泌中的作用仍有待研究。在本研究中，我们证明抵抗素可诱导PC3细胞迁移和侵袭增加。此外，这些现象伴随着抵抗素处理的PC3细胞中磷酸化粘着斑激酶（p-FAK）水平升高以及基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）分泌增加。有趣的是，在自分泌刺激模型中，从抵抗素处理的PC3细胞上清液中分离出的EVs可诱导迁移和侵袭增加，并伴有高MMP-2和MMP-9分泌。总之，我们的数据首次证明抵抗素可诱导迁移和侵袭，部分是通过在PC3细胞中分泌具有促侵袭特性的EVs来实现的。
