Colon cancer, mechanism underlying metastasis discovered
New discovery on the colon cancer with metastases. This disease is the third leading cause of cancer death worldwide. Thanks to a study conducted by the “Adriano Buzzati Traverso” Institute of Genetics and Biophysics of the CNR of Naples, two markers have been identified that induce colon cancer stem cells to develop metastases. This opens the way to new therapies which, by targeting these factors, could selectively eliminate a specific population of cancer cells. The results of the research carried out with the support of the AIRC Foundation for Cancer Research have been published in the journal Theranostics.
Colon tumors, metastases often already present at the time of diagnosis
“The colorectal cancer is currently the third cause of cancer death worldwide. From i principali risk factors for the disease there are theage, a little varied diet and unbalanced, the smoke ed random errors in DNA occurring during cell division. Some of the most frequent genetic mutations in this type of tumor can cause uncontrolled cell growth of the cells themselves ”. Thus Enza Lonardo of Cnr-Igb.
“Our study has identified a subpopulation of cancer stem cells – continues the researcher – characterized by the high expression of the adhesion molecule L1cam. The co-expression of this factor with the Cxcr4 receptor, known to favor the migration of tumor cells to distant organs, increases the tumorigenic potential of tumor stem cells, making them highly resistant to chemotherapy treatment and favoring the onset of metastases, particularly in liver”.
“Although considerable progress has been made in the understanding of cancer biology in recent decades, the efficacy of treatments available for colorectal cancer has not improved significantly, and unfortunately an increasing number of patients at the time of diagnosis he already has liver metastases”.
Colon cancer with metastases: cancer stem cells and relapses
The identification of specific molecular targets can be decisive in determining the most suitable treatment for each patient. “Several studies are currently focused on cancer stem cells – explains Lonardo – as their involvement in promoting tumor growth and the development of metastases has been demonstrated. Furthermore, cancer stem cells are generally highly resistant to chemotherapy and can consequently be responsible for the recurrence of the disease ”.
Colon cancer discovered: development of new drugs possible
Researchers also identified some molecular mechanisms underlying the high coexpression of these markers. They are absent in normal colon cells, while they are activated in tumor cells residing in an oxygen-poor microenvironment and in the presence of the Nodal molecule. The presence of both factors (hypoxia and Nodal) induces the expression of L1cam and Cxcr4, thus promoting the onset of a more aggressive and less responsive phenotype to conventional drug therapies.
The study made use of the use of three-dimensional cellular models, the organoids, deriving from cancer cells of patients, which made it possible to reproduce in the laboratory the architecture and the essential biological characteristics of colorectal cancers. “This discovery could allow the development of new drugs that act in a specific way both through the direct reduction of the expression of the two markers, and indirectly on the tumor microenvironment – concludes Lonardo – for example by increasing the oxygenation of the tumor mass or by modulating the signaling pathway mediated by Nodal. These new approaches could have important clinical implications, in drastically reducing the tumorigenic potential of cells and consequently drastically reducing recurrence and the formation of metastases ”.