Identification of intratumoral bacteria that enhance breast tumor metastasis
ABSTRACT The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understoo...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2025-03-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03595-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850225449648521216 |
|---|---|
| author | Zachary J. Gerbec Antonio Serapio-Palacios Avril Metcalfe-Roach Zakhar Krekhno Haggai Bar-Yoseph Sarah E. Woodward Jorge Pena-Díaz Oksana Nemirovsky Shannon Awrey Sebastian H. Moreno Sean Beatty Esther Kong Nina Radisavljevic Mihai Cirstea Shawn Chafe Paul C. McDonald Sam Aparicio B. Brett Finlay Shoukat Dedhar |
| author_facet | Zachary J. Gerbec Antonio Serapio-Palacios Avril Metcalfe-Roach Zakhar Krekhno Haggai Bar-Yoseph Sarah E. Woodward Jorge Pena-Díaz Oksana Nemirovsky Shannon Awrey Sebastian H. Moreno Sean Beatty Esther Kong Nina Radisavljevic Mihai Cirstea Shawn Chafe Paul C. McDonald Sam Aparicio B. Brett Finlay Shoukat Dedhar |
| author_sort | Zachary J. Gerbec |
| collection | DOAJ |
| description | ABSTRACT The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understood. To identify tumor-associated bacteria and their role in metastasis, we utilized established murine models of non-metastatic and metastatic breast tumors to identify bacteria capable of driving metastatic disease. We found several species of the Bacillus genus that were unique to metastatic tumors, and found that breast tumor cells cultured with a Bacillus bacterium isolated from metastatic tumors, Bacillus thermoamylovorans, produced nearly 3× the metastatic burden as control cells or cells cultured with bacteria from non-metastatic breast tumors. We then performed targeted metabolomics on tumor cells cultured with different bacterial species and found that B. thermoamylovorans differentially regulated tumor cell metabolite profiles compared to bacteria isolated from non-metastatic tumors. Using these bacteria, we performed de novo sequencing and tested for the presence of genes that were unique to the bacterium isolated from metastatic tumors in a patient population to provide a proof-of-concept for identifying how specific bacterial functions are associated with the metastatic process in cancer independent of bacterial species. Together, our data directly demonstrate the ability of specific bacteria to promote metastasis through interaction with cancer cells.IMPORTANCEMetastasis is a major barrier to long-term survival for cancer patients, and therapeutic options for patients with aggressive, metastatic forms of breast cancer remain limited. It is therefore critical to understand the differences between non-metastatic and metastatic disease to identify potential methods for slowing or even stopping metastasis. In this work, we identify a bacterial species present with metastatic breast tumors capable of increasing the metastatic capabilities of tumor cells. We isolated and sequenced this bacteria, as well as a control species which failed to promote metastasis, and identified specific bacterial genes that were unique to the metastasis-promoting species. We tested for the presence of these bacterial genes in patient tumor samples and found they were more likely to be associated with mortality. We also identified enrichment of specific bacterial functions, providing insight into possible sources of bacteria-driven increases in the metastatic potential of multiple cancer types. |
| format | Article |
| id | doaj-art-a92d26780adf4507a19ee5a6cb9fffdf |
| institution | OA Journals |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-a92d26780adf4507a19ee5a6cb9fffdf2025-08-20T02:05:21ZengAmerican Society for MicrobiologymBio2150-75112025-03-0116310.1128/mbio.03595-24Identification of intratumoral bacteria that enhance breast tumor metastasisZachary J. Gerbec0Antonio Serapio-Palacios1Avril Metcalfe-Roach2Zakhar Krekhno3Haggai Bar-Yoseph4Sarah E. Woodward5Jorge Pena-Díaz6Oksana Nemirovsky7Shannon Awrey8Sebastian H. Moreno9Sean Beatty10Esther Kong11Nina Radisavljevic12Mihai Cirstea13Shawn Chafe14Paul C. McDonald15Sam Aparicio16B. Brett Finlay17Shoukat Dedhar18Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaDepartment of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaDepartment of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaDepartment of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaDepartment of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaMichael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, CanadaDepartment of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, CanadaABSTRACT The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understood. To identify tumor-associated bacteria and their role in metastasis, we utilized established murine models of non-metastatic and metastatic breast tumors to identify bacteria capable of driving metastatic disease. We found several species of the Bacillus genus that were unique to metastatic tumors, and found that breast tumor cells cultured with a Bacillus bacterium isolated from metastatic tumors, Bacillus thermoamylovorans, produced nearly 3× the metastatic burden as control cells or cells cultured with bacteria from non-metastatic breast tumors. We then performed targeted metabolomics on tumor cells cultured with different bacterial species and found that B. thermoamylovorans differentially regulated tumor cell metabolite profiles compared to bacteria isolated from non-metastatic tumors. Using these bacteria, we performed de novo sequencing and tested for the presence of genes that were unique to the bacterium isolated from metastatic tumors in a patient population to provide a proof-of-concept for identifying how specific bacterial functions are associated with the metastatic process in cancer independent of bacterial species. Together, our data directly demonstrate the ability of specific bacteria to promote metastasis through interaction with cancer cells.IMPORTANCEMetastasis is a major barrier to long-term survival for cancer patients, and therapeutic options for patients with aggressive, metastatic forms of breast cancer remain limited. It is therefore critical to understand the differences between non-metastatic and metastatic disease to identify potential methods for slowing or even stopping metastasis. In this work, we identify a bacterial species present with metastatic breast tumors capable of increasing the metastatic capabilities of tumor cells. We isolated and sequenced this bacteria, as well as a control species which failed to promote metastasis, and identified specific bacterial genes that were unique to the metastasis-promoting species. We tested for the presence of these bacterial genes in patient tumor samples and found they were more likely to be associated with mortality. We also identified enrichment of specific bacterial functions, providing insight into possible sources of bacteria-driven increases in the metastatic potential of multiple cancer types.https://journals.asm.org/doi/10.1128/mbio.03595-24tumor microbiomemetastasiscancerintratumoral bacteriaBacillus |
| spellingShingle | Zachary J. Gerbec Antonio Serapio-Palacios Avril Metcalfe-Roach Zakhar Krekhno Haggai Bar-Yoseph Sarah E. Woodward Jorge Pena-Díaz Oksana Nemirovsky Shannon Awrey Sebastian H. Moreno Sean Beatty Esther Kong Nina Radisavljevic Mihai Cirstea Shawn Chafe Paul C. McDonald Sam Aparicio B. Brett Finlay Shoukat Dedhar Identification of intratumoral bacteria that enhance breast tumor metastasis mBio tumor microbiome metastasis cancer intratumoral bacteria Bacillus |
| title | Identification of intratumoral bacteria that enhance breast tumor metastasis |
| title_full | Identification of intratumoral bacteria that enhance breast tumor metastasis |
| title_fullStr | Identification of intratumoral bacteria that enhance breast tumor metastasis |
| title_full_unstemmed | Identification of intratumoral bacteria that enhance breast tumor metastasis |
| title_short | Identification of intratumoral bacteria that enhance breast tumor metastasis |
| title_sort | identification of intratumoral bacteria that enhance breast tumor metastasis |
| topic | tumor microbiome metastasis cancer intratumoral bacteria Bacillus |
| url | https://journals.asm.org/doi/10.1128/mbio.03595-24 |
| work_keys_str_mv | AT zacharyjgerbec identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT antonioserapiopalacios identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT avrilmetcalferoach identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT zakharkrekhno identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT haggaibaryoseph identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT sarahewoodward identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT jorgepenadiaz identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT oksananemirovsky identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT shannonawrey identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT sebastianhmoreno identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT seanbeatty identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT estherkong identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT ninaradisavljevic identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT mihaicirstea identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT shawnchafe identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT paulcmcdonald identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT samaparicio identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT bbrettfinlay identificationofintratumoralbacteriathatenhancebreasttumormetastasis AT shoukatdedhar identificationofintratumoralbacteriathatenhancebreasttumormetastasis |