Effect of exercise on peritoneal microenvironment and progression of ovarian cancer.
Effect of exercise on peritoneal microenvironment and progression of ovarian cancer.
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发表时间：
2021
影响因子：
5.3
通讯作者：
M. J. Morrisson;Fangfang Bi;Kevin Yang;S. Cady;T. Hartwich;Alexandra P Cerchia;Zhigui Li;Jaeyeon Kim;M. Irwin;Yang Yang-Hartwich-Yang
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作者：
M. J. Morrisson;Fangfang Bi;Kevin Yang;S. Cady;T. Hartwich;Alexandra P Cerchia;Zhigui Li;Jaeyeon Kim;M. Irwin;Yang Yang-Hartwich-Yang
卵巢癌是最致命的妇科恶性肿瘤之一，缺乏不会显著影响患者健康相关生活质量的治疗方法。运动与降低癌症风险和改善临床结果有关;然而，潜在的分子机制尚不清楚。在这项研究中，我们利用跑步机运动模型来研究运动对高级别浆液性卵巢癌（HGSOC）进展和化疗结果的影响。我们发现，在同基因小鼠卵巢癌模型中，跑步跑步可以抑制肿瘤的腹膜定植。急性运动刺激了腹腔微环境中CCL 2和IL-15的产生，同时下调了CCL 22、VEGF和CCL 12。使用共培养模型，我们证明了CCL 2在介导腹膜细胞活性以抑制癌细胞活力中的作用。我们发现，M1巨噬细胞的激活可能有助于运动引起的腹膜微环境的变化。我们发现，长期运动调节与脂质形成、产热、布朗宁和炎症相关的腹膜内脂肪组织的基因表达，这有助于抑制转移性卵巢癌的定植。在小鼠模型中，跑步机跑步还降低了血液尿素氮水平，减少了化疗期间中性粒细胞减少症和血小板减少症的发生率，这表明运动在改善化疗结果方面具有潜在的有益作用。我们的数据提供了新的见解，急性和慢性影响的身体活动对卵巢癌在分子和体内水平。
Ovarian cancer is one of the deadliest gynecological malignancies and lacks treatments that do not significantly impact patient health-related quality of life. Exercise has been associated with reduced cancer risk and improved clinical outcomes; however the underlying molecular mechanisms are unknown. In this study, we utilized a treadmill-running exercise model to investigate the effects of exercise on high-grade serous ovarian carcinoma (HGSOC) progression and chemotherapy outcomes. We found that treadmill-running suppressed peritoneal colonization of tumors in a syngeneic mouse ovarian cancer model. Acute exercise stimulated the production of CCL2 and IL-15 in the peritoneal microenvironment while downregulating CCL22, VEGF, and CCL12. Using a co-culture model, we demonstrated the role of CCL2 in mediating the activity of peritoneal cells to inhibit cancer cell viability. We showed that the activation of M1 macrophages may contribute to the exercise-induced changes in the peritoneal microenvironment. We identified that chronic exercise modulates gene expression of intraperitoneal fat tissues related to lipid formation, thermogenesis, browning, and inflammation, which can contribute to inhibiting the colonization of metastatic ovarian cancer. Treadmill running also lowered blood urea nitrogen levels and reduced incidence of neutropenia and thrombocytopenia during chemotherapy in a mouse model, suggesting the potential beneficial effects of exercise in improving chemotherapy outcomes. Our data provided new insights into the acute and chronic effects of physical activity on ovarian cancer at the molecular and in vivo levels.