Abstract
Intracellular bacteria in a spontaneous breast cancer model promote metastatic colonization.
Major Finding: Intracellular bacteria in a spontaneous breast cancer model promote metastatic colonization.
Concept: These bacteria modulate the cellular actin network and promote cell survival against fluid sheer stress.
Impact: These results strongly implicate targeting these microbiota as an early way of treating metastasis.
Recent lines of evidence suggest that microbes, in addition to being critical components of the gut, are also important parts of the tumor tissue itself. However, the biological roles that these tissue-resident microbes play within spontaneous tumor progression remain to be determined. To address this, Fu and colleagues sought to characterize the intracellular bacteria in a spontaneous murine breast cancer model. After optimizing for the low biomass of the intratumor microbiota, it was found that tumor tissue harbors a higher number of bacteria per gram of tissue as compared to the normal breast and showed an enrichment in Staphylococcus, Lactobacillus, Enterococcus, and Streptococcus genera. Diversity of species was also reduced in tumor tissues, suggesting selection and expansion of select microbes. Investigation into the location of these microbes showed their presence mainly in epithelial cells versus stromal cells, with high-resolution electron microscopy indicating cytosolic localization. Selective depletion of intratumor bacteria did not show a change to primary tumor weight but did reduce lung metastases in this mouse model with additional analyses indicating that these intracellular bacteria traveled along with tumor cells to the metastatic sites. Evaluation of the individual bacterial strains that exert tumorigenic effects revealed that certain strains (including S. xylosus, L. animalis, and S. cuniculi) that demonstrate the ability to invade tumor cells also contributed to increased lung metastasis with no effect on primary tumor growth, while those with low invasion efficiency (such as E. faecalis) did not share this phenotype. Mechanistically, these intratumoral bacteria were found to contribute to cancer cell metastatic colonization by triggering the fluid shear stress pathway and actin cytoskeleton reorganization. Finally, a similar microbial community was observed in human breast tumors, suggesting a conserved role in cancer pathogenesis and progression. Collectively, these data demonstrate the critical role that intratumoral bacteria play in metastasis and suggest their use as a potential target to prevent metastasis at an early stage.
Note:Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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