Blood vessels, bacteria, cancer: a study by Humanitas University, published in Cancer Cell, provides new answers on the formation of metastases in the liver
A study signed by Prof. Maria Rescigno professor of General Pathology and Deputy Pro-Rector for research at Humanitas University, and Dr. Alice Bertocchi, carried out in collaboration between Humanitas University and IEO (European Institute of Oncology), has been published in the prestigious scientific journal Cancer Cell. The study is part of the AIRC 5×1000 project ‘Immunity in Cancer Spreading and Metastasis’ (ISM).
The research shows that metastasis from the primary tumour (colorectal cancer) to the liver depends on four events: the modification of the intestinal vascular barrier, given the identification of a biomarker; the migration of bacteria of the microbiota from the primary tumour to the liver, given the identification of the bacterium responsible; the formation of a premetastatic niche in the liver and lastly the recall of the tumour cells in the liver and the beginning of the metastasis process.
“Metastasis of a colon tumour normally occurs through the draining lymph nodes in the liver or lungs. Therefore, after the operation to remove the tumour, we check if the draining lymph nodes are affected by the disease. If so, we consider the patient to be metastatic and start a more aggressive therapy,” explains Prof. Rescigno. “The problem arises when the patient, even with no signs of metastases in the lymph node, later develops metastases in the liver. We have been asking ourselves what causes this phenomenon“.
The starting hypothesis is that the cells do not reach the liver through the lymphatic vessels but through the blood vessels. “We’ve asked ourselves how this could happen. To understand this, we analysed the vessels of patients through a retrospective study of the tissue of patients who were operated a few years ago. The vessels of the intestine are organised in such a way that they do not allow bacteria to pass through: they form a ‘barrier’ to keep them out. But there are cases where bacteria spread, as in the case of salmonella reaching the liver. In these cases we know that there is a marker that indicates when the barrier becomes permeable,” Prof. Rescigno points out. “Starting from these assumptions, we verified that all patients with liver metastases saw an increase of this marker already in the primary tumour, so before metastases could be seen”.
“The next step was to ask ourselves the following question: if intestinal permeability can be modified by bacteria, does a bacteria increase in the tumour site modify the barrier and promote metastasis? We found that bacteria are able to “enter” the tumour, modify the barrier, migrate to the liver and create a pre-metastatic niche that acts as a “lure” for tumour cells. This is a very important discovery, which allowed us to identify the bacterium capable of triggering this process,” she concludes. “Moreover, thanks to the PV1 marker, we can now predict whether a subject will metastasise to the liver or not, and thus decide on the type of treatment and how far apart the follow-ups should be”.