Hillers-Ziemer Lauren E, Williams Abbey E, Janquart Amanda, Grogan Caitlin, Thompson Victoria, Sanchez Adriana, Arendt Lisa M
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Program in Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cancers (Basel). 2021 Feb 28;13(5):1005. doi: 10.3390/cancers13051005.
Obesity is correlated with increased incidence of breast cancer metastasis; however, the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obese mouse model, obesity enhanced lung metastasis in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of premetastatic niches formed by primary tumors. Lung stromal cells isolated from obese tumor-naïve mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers and transforming growth factor beta-1 (TGFβ1). Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to colony-stimulating factor 2 (CSF2) expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive to metastatic growth.
肥胖与乳腺癌转移发生率增加相关；然而，肥胖促进转移的潜在机制尚不清楚。在饮食诱导的肥胖小鼠模型中，无论有无原发性乳腺肿瘤，肥胖都会增强肺转移，并增加髓系细胞向肺部的募集。在没有肿瘤的情况下，肥胖小鼠肺部基质中的髓系细胞数量增加，胶原纤维增多，这让人联想到原发性肿瘤形成的前转移微环境。从未接触过肿瘤的肥胖小鼠中分离出的肺基质细胞显示出增殖、收缩能力增强，以及细胞外基质、炎症标志物和转化生长因子β1（TGFβ1）的表达增加。肥胖小鼠肺基质细胞的条件培养基在体外促进了髓系细胞对集落刺激因子2（CSF2）表达的迁移反应，并增强了肿瘤细胞的侵袭。总之，这些结果表明，在肿瘤形成之前，肥胖会改变肺微环境，形成有利于转移生长的小生境。
