Chan Alfred A, Caron Christine, Navarrete Marian, Lee Calvin K, Noguti Juliana, Bui Jack D, Lee Delphine J
The Lundquist Institute, Torrance, CA, USA.
Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0612, USA.
Transl Oncol. 2025 Sep;59:102451. doi: 10.1016/j.tranon.2025.102451. Epub 2025 Jun 25.
Studies have reported differences in specific bacteria comparing the tissue microbiome in human breast cancer versus normal breast tissue, prompting hypotheses for potential therapies or theragnosis. To test these hypotheses using controlled experiments animal models are needed. Therefore, we investigated the microbiome in the gut and mammary tissue in a mouse model of breast cancer. C57BL/6 mice expressing the polyoma middle T antigen in the mammary gland (PyMT) develop spontaneous multifocal breast tumors. Microbiota in the gut and mammary tissue were studied prior to and after development of mammary gland tumors by amplicon and shotgun DNA sequencing. In parallel, RNA sequencing was performed on tumor and normal tissue to measure differences in gene expression associated with breast cancer. Bacteria identified in these studies were administered to mice to test their effects on cancer progression. Bacterial community composition in the gut of healthy or tumor-bearing mice showed wide fluctuation over time and did not organize into discrete clusters. In tumor versus healthy mammary gland tissue, relative abundances of six bacteria were significantly different: Ralstonia, Methylobacterium, Pelomonas, Staphylococcus and Tepidimonas. Methlyobacterium sequences were significantly higher (PERMANOVA, P = 0.013) in healthy tissue when compared to tumor, leading to a hypothesis that Methylobacterium may promote health. When co-transplanted with breast tumor cells, Methylobacterium reduced growth in immune competent mice. Here we describe the gut and mammary tissue microbial composition of healthy and breast tumor-bearing animals, identifying Methylobacterium sp as a commensal bacteria that might have therapeutic potential to reduce breast cancer progression.
研究报告了在人类乳腺癌组织微生物群与正常乳腺组织中特定细菌的差异，这引发了关于潜在治疗方法或治疗诊断的假设。为了通过对照实验来验证这些假设，需要动物模型。因此，我们在乳腺癌小鼠模型中研究了肠道和乳腺组织中的微生物群。在乳腺中表达多瘤病毒中间T抗原（PyMT）的C57BL/6小鼠会自发形成多灶性乳腺肿瘤。通过扩增子和鸟枪法DNA测序研究了乳腺肿瘤发生前后肠道和乳腺组织中的微生物群。同时，对肿瘤组织和正常组织进行RNA测序，以测量与乳腺癌相关的基因表达差异。将这些研究中鉴定出的细菌接种到小鼠体内，以测试它们对癌症进展的影响。健康小鼠或荷瘤小鼠肠道中的细菌群落组成随时间呈现出很大的波动，并未形成离散的簇。在肿瘤乳腺组织与健康乳腺组织中，六种细菌的相对丰度存在显著差异：罗尔斯通氏菌、甲基杆菌属、皮氏菌属、葡萄球菌属和嗜温单胞菌属。与肿瘤组织相比，健康组织中的甲基杆菌属序列显著更高（PERMANOVA，P = 0.013），这引发了一种假设，即甲基杆菌属可能促进健康。当与乳腺肿瘤细胞共同移植时，甲基杆菌属可减少免疫功能正常小鼠体内肿瘤的生长。在此，我们描述了健康和荷乳腺肿瘤动物的肠道和乳腺组织微生物组成，确定甲基杆菌属为一种共生细菌，可能具有降低乳腺癌进展的治疗潜力。
