▎ WuXi AppTec content team editor
The microbes in our bodies do not affect physiological functions all the time, and more and more evidence shows that microorganisms, including intestinal bacteria, regulate our physiological behavior in many ways, and even transmit specific signals to the brain through the gastrointestinal vagus nerve. In the field of oncology, microorganisms are also one of the objects of focus of scientists.
What most current studies have found is that microorganisms have the phenomenon of regulating cancer susceptibility and tumor progression. They usually do not play a direct role, but affect tumorigenesis by influencing some metabolic and immune system signaling pathways, and generally act on adjacent tumor tissue.
With the development of sequencing technology, some scientists in Israel and the United States have shown that microbes do not just indirectly affect tumors, but are more likely to be part of tumors. A few days ago, Cai Shang's research group in the School of Life Sciences of Westlake University published an article in "Cell", which not only reaffirmed the existence of bacteria in tumors, but also proved for the first time that unique intracellular bacteria in breast cancer play a key role in tumor metastasis and colonization.
Intracellular bacteria of tumors can help them metastasize (Image source: Reference[2])
In the new study, Dr. Cai and colleagues constructed a batch of breast cancer model mice filled with tissues filled with large numbers of bacteria, somewhat similar to the phenomenon observed in human breast cancer. Intuitively, the number of bacteria in breast cancer tissue is about 10 times that of normal breast tissue.
Even more surprising is that many of these bacteria colonize the cell fluid of cancer cells, that is, inside the cells. The bacteria inside these cancer cells are even alive and die gradually in a cell-permeable antibiotic environment.
▲ Antibiotic clearance experiments prove that tumor flora is essential for tumor metastasis (Image source: Reference[2])
They observed that as cancer cells wandered around the circulatory system, the bacteria followed them throughout the body. These bacteria appear to be able to regulate the cell's actin network and help cancer cells cope with mechanical stress during migration, improving survival.
In the study tests, the bacteria in the cancer cells appeared to specifically help the cancer cells metastasize, but had little effect on the growth of the in situ tumor. By injecting the mice with a compound antibiotic in the tail vein, they attempted to specifically clear the tumor flora. When the tumor flora is removed, the size of the tumor itself does not shrink as a result, but the lung metastases are significantly reduced, which shows that these bacteria are very critical to tumor metastasis.
▲ Tumor cells carry bacteria to distant organs and promote metastasis (Image source: Reference[2])
The study managed to collect tumor flora in the peripheral blood, and when these bacteria were reinfused back into tumor mice, the tumor growth process in situ had little effect, but the level of tumor metastasis began to increase significantly, and even tumor types that rarely metastasized began to metastasize in large quantities.
One of the most important things bacteria do in metastasis is to help cancer cells resist mechanical stress, which is routinely susceptible to death by a mechanical force called flow shear pressure as they move with the bloodstream. But bacteria are able to reshape the cytoskeleton, enhance their ability to resist fluid pressure, and make it easier for tumors to metastasize.
This "symbiotic" relationship is really amazing, as if the bacteria reside in the tumor and then help the tumor metastasize. Study corresponding author Dr. Cai Shang told us that it is not clear why bacteria are enriched in tumors and the source of bacteria, which may be related to the immunosuppressive environment of tumors, but may also involve more complex mechanisms, such as the non-biological environment of tumors, metabolic environment, etc.
Image credit: 123RF
Although studies have confirmed that intracellular bacteria play an important role in cancer metastasis, the research team does not rule out the possibility that these bacteria affect the progression of in situ cancer.
We may be more concerned about whether this research can help us fight and treat tumors. Dr. Cai Shang pointed out that there are already some studies suggesting that the microbiota information in the blood can help diagnose tumorigenesis, and the use of blood flora to determine cancer metastasis is a very worthy direction for exploration in the future.
The research team hopes to collect evidence of the relationship between tumor flora and tumor progression at the clinical level, develop new methods for regulating tumor flora, and explore the deep mechanism of tumor microbiota interaction.
Cai Shang's research group mainly focuses on the breast gland as a model organ, and explores the maintenance of specific structural functions of breast stem cells during adolescence, pregnancy and lactation, as well as the important role of breast cancer stem cells in the occurrence, development, drug resistance, recurrence and metastasis of cancer. Recent research has opened up a new tumor research direction for the physiological function of tumor microbiota, which is an emerging field full of unknowns, and looks forward to the addition of excellent postdocs interested in discussing tumor microbiota to jointly solve the mystery of the interaction between microorganisms and cancer cells.
Lab webpage: https://www.cai-lab.com
Resources:
[1] Evidence in mice that bacteria in tumors help cancer cells metastasize. Retrieved Apr 7th, 2022 from https://www.eurekalert.org/news-releases/948302
[2] Aikun Fu , B. et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell (2022), DOI: 10.1016/j.cell.2022.02.027
[3] Nejman, D. et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 368, 973-980, doi:10.1126/science.aay9189 (2020).
[4] Riquelme, E. et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell 178, 795-806 e712, doi:10.1016/j.cell.2019.07.008 (2019).
[5] Jin, C. et al. Commensal Microbiota Promote Lung Cancer Development via gammadelta T Cells. Cell 176, 998-1013 e1016, doi:10.1016/j.cell.2018.12.040 (2019).
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