Jayasinghe Mevan M, Golden Jacqueline M, Nair Priyanka, O'Donnell Cara M, Werner Michael T, Kurt Robert A
Department Biology, Lafayette College, Easton, PA 18042, USA.
Breast Cancer Res Treat. 2008 Oct;111(3):511-21. doi: 10.1007/s10549-007-9802-6. Epub 2007 Nov 3.
Besides functioning as a chemotactic factor, CCL5 has been associated with progression of disease in women with breast cancer, immune modulation and metastasis. Here we asked whether CCL5 produced by tumor cells contributed to growth or metastasis of breast cancer. For this purpose, we used two murine mammary carcinomas, the 4T1 tumor which is metastatic and constitutively expresses CCL5, and the 168 tumor which is not metastatic and does not constitutively express CCL5. RNA interference was used to inhibit CCL5 expression from the 4T1 tumor, and a CCL5 transgene was used to express CCL5 by the 168 tumor. Six different clones of 4T1 that exhibited stable reduction in CCL5 expression, and three different clones of 168 that exhibited stable CCL5 expression were compared to the parental tumors and vector transfected controls. Significantly, in both models, tumor-derived CCL5 expression did not correlate with MHC expression, growth rate, or metastatic ability of the tumors. These results show that tumor-derived CCL5 expression alone does not make a significant contribution to breast cancer progression.
除了作为一种趋化因子发挥作用外，CCL5还与乳腺癌女性患者的疾病进展、免疫调节和转移有关。在此，我们探讨肿瘤细胞产生的CCL5是否促进乳腺癌的生长或转移。为此，我们使用了两种小鼠乳腺癌模型，具有转移能力且组成性表达CCL5的4T1肿瘤，以及不具有转移能力且不组成性表达CCL5的168肿瘤。利用RNA干扰抑制4T1肿瘤中的CCL5表达，并通过168肿瘤的CCL5转基因来表达CCL5。将6个CCL5表达稳定降低的4T1不同克隆，以及3个CCL5表达稳定的168不同克隆，与亲本肿瘤和载体转染对照进行比较。值得注意的是，在这两种模型中，肿瘤来源的CCL5表达均与肿瘤的MHC表达、生长速率或转移能力无关。这些结果表明，仅肿瘤来源的CCL5表达对乳腺癌进展没有显著贡献。
