脂肪源性细胞趋化因子CCL7和CCL8促进乳腺癌侵袭转移的分子机制

脂肪细胞大量存在于乳腺癌微环境中，参与微环境重塑并促进乳腺癌发展。脂肪细胞除了通过直接相互作用影响癌细胞，也能通过分泌多种胞外细胞因子发挥作用。然而，以往的研究主要集中于激素类脂肪因子，对趋化因子在脂肪细胞-癌细胞相互作用中的功能尚了解有限。本课题组的前期研究表明，脂肪细胞能在体外促进乳腺癌细胞的迁移和侵袭；高通量测序（RNA-Seq）和荧光定量PCR结果显示，脂肪细胞与乳腺癌细胞共培养后细胞趋化因子CCL7和CCL8表达明显上调。据此，本项目拟以脂肪源性趋化因子CCL7和CCL8为研究对象，研究其在脂肪细胞介导的乳腺癌细胞侵袭和转移中的作用与分子机制，并为乳腺癌的临床诊断与治疗提供理论依据。

Adipocyte is one of the most abundant cell types in breast cancer microenvironment, contributing to the microenvironment re-organization and breast cancer progression. Breast cancer cell-activated adipocytes can not only provide energy for tumor cell growth and proliferation, but also promote tumorigenesis by secreting a variety of cytokines, which act on both cancer microenvironment and cancer cells. With this regard, adipokines have been extensively investigated, but the roles and mechanisms of chemokines in adipocyte-tumor cell interaction are less well understood. Previously, we found that adipocytes were capable of promoting migration and invasion of breast cancer cells in vitro. In addition, transcriptome sequencing (RNA-Seq) and quantitative RT-PCR analysis identified the expression of chemokine CCL7 and CCL8 in adipocytes was significantly enhanced upon co-culture with breast cancer cells. Therefore, we plan to investigate in this proposal the roles and molecular mechanisms of adipocyte-derived CCL7 and CCL8 in invasion and metastasis of breast cancer cells. The results are expected to provide a theoretical basis for clinical diagnosis and breast cancer therapy.