PDF(Pubmed)
Abstract：
Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. To examine the impact of weight loss on the mammary microenvironment, mice were fed high-fat diet to induce obesity, then switched to a low-fat diet. In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. When TC2 tumor cells were mixed with CD11b+CD34+ myeloid progenitor cells, collagen deposition within the tumors was significantly greater compared to when tumor cells were mixed with CD11b+CD34- monocytes, suggesting that fibrocytes contribute to early collagen deposition in mammary tumors of obese mice. Overall, these studies show that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression.
摘要：
肥胖是乳腺癌的危险因素,患乳腺癌的肥胖女性预后恶化。在乳腺内，肥胖导致慢性，巨噬细胞驱动的炎症和脂肪组织纤维化。为了检查体重减轻对乳腺微环境的影响，高脂饮食诱导小鼠肥胖，然后改用低脂饮食.在以前肥胖的老鼠中，我们观察到乳腺中的冠状结构和纤维细胞数量减少，而胶原蛋白沉积并未随体重减轻而解决。在将TC2肿瘤细胞移植到瘦乳腺中之后，肥胖，和以前肥胖的老鼠，与肥胖小鼠相比,在先前肥胖小鼠的肿瘤中观察到胶原沉积和癌症相关成纤维细胞减少.当TC2肿瘤细胞与CD11b+CD34+骨髓祖细胞混合时，当肿瘤细胞与CD11b+CD34-单核细胞混合时，肿瘤内的胶原沉积明显更大，表明纤维细胞有助于肥胖小鼠乳腺肿瘤的早期胶原沉积。总的来说,这些研究表明，体重减轻解决了乳腺内一些可能导致肿瘤进展的微环境条件。
