Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer

0301 basic medicine 0303 health sciences Lung Neoplasms Microbiota Breast Neoplasms Neoplastic Cells, Circulating 3. Good health Mice 03 medical and health sciences Cell Line, Tumor Animals Humans Female Neoplasm Metastasis
DOI: 10.1016/j.cell.2022.02.027 Publication Date: 2022-04-07T14:35:59Z
ABSTRACT
Tumor-resident intracellular microbiota is an emerging tumor component that has been documented for a variety of cancer types with unclear biological functions. Here, we explored the functional significance of these intratumor bacteria, primarily using a murine spontaneous breast-tumor model MMTV-PyMT. We found that depletion of intratumor bacteria significantly reduced lung metastasis without affecting primary tumor growth. During metastatic colonization, intratumor bacteria carried by circulating tumor cells promoted host-cell survival by enhancing resistance to fluid shear stress by reorganizing actin cytoskeleton. We further showed that intratumor administration of selected bacteria strains isolated from tumor-resident microbiota promoted metastasis in two murine tumor models with significantly different levels of metastasis potential. Our findings suggest that tumor-resident microbiota, albeit at low biomass, play an important role in promoting cancer metastasis, intervention of which might therefore be worth exploring for advancing oncology care.
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