An investigation published in The Journal of Clinical Investigation by the group of Dr. Maria Caffarel, Ikerbasque Researcher and Miguel Servet, and Head of the Breast Cancer Group at the Biodonostia Health Research Institute, shows for the first time that the proinflammatory cytokine Oncostatin M (OSM) favors the progression of breast cancer and metastasis, acting as a messenger between different populations of the tumor microenvironment.
Tumors are not only composed of cancer cells, but also contain, among others, cells of the immune system, endothelial cells that form blood vessels, and fibroblasts, which have traditionally been considered support cells. Sometimes these cells, which make up what we call the tumor microenvironment, help the tumor progress. Understanding how different cell populations communicate with each other is key to designing effective strategies against cancer. Cytokines are molecules that are generally used by cells of the immune system to send signals. The IIS Biodonostia breast cancer group has found that the OSM cytokine is a messenger used by the different populations of the tumor microenvironment to communicate with cancer cells.
“Through the OSM pathway, a kind of “menage-à-trois” is established between cancer cells, immune system macrophages and tumor-associated fibroblasts, which favors breast cancer progression and metastasis” explains Caffarel. The first step was to block the OSM pathway and its receptor in animal models of breast cancer.
"We observed that when this pathway was silenced, breast tumors grew less, were less aggressive and the number of mice with lung metastases was very significantly reduced" sais Angela Araujo, first signatory of the study, adding that " when we blocked this pathway only in the tumor microenvironment, and not in cancer cells, we saw the same effect, which confirmed for us that the microenvironment was very important in signaling by OSM.”
According to the results of the research, signed by researchers Angela Araujo and Andrea Abaurrea as first authors, tumors with high levels of OSM are associated with a worse prognosis in patients who had them, opening a new possible path of treatment that worth exploring.
"In fact, there are already clinical trials for other pathologies that are investigating the use of antibodies that block OSM and its receptor OSMR. Our study supports that these antibodies can be evaluated in clinical trials for breast cancer", concludes Andrea Abaurrea.
This work has been the result of the collaboration of basic and clinical research groups from national centers (IIS Biodonostia and Fundación Ikerbasque, IBBTEC, CICbioGUNE, Universidad Complutense and CIBERONC) and international centers (University Hospital of Basilea, Switzerland; Technological University of Sidney, Australia; University of Cambridge and Institute of Cancer Research, UK).
For more information: https://doi.org/10.1172/JCI148667
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