Tumor cell surrounded by platelets. Credit score: Marta Hergueta / CNIO.
Weight problems is related to an elevated threat of creating breast most cancers, and a better chance for the most cancers to unfold to different organs. However the causes of this affiliation are nonetheless not properly understood. Researchers on the Spanish Nationwide Most cancers Analysis Heart (CNIO) have now offered new information by discovering {that a} high-fat weight-reduction plan prompts mechanisms that facilitate metastasis.
It is a research led by Héctor Peinado, head of the CNIO’s Microenvironment and Metastasis Group, performed in animal fashions of triple-negative breast most cancers that develop lung metastasis. It has been printed in Nature Communications.
For most cancers to unfold to different organs, many tumor cells should go away the first tumor, journey by the bloodstream, nest and proliferate in one other organ. Typically the first tumor sends molecules that modify the goal organ prematurely, and prepares the equal of a nest that hosts the tumor cells: that is the so-called “premetastatic niche,” by which the tumor cell can take root and develop metastases.
The CNIO group reveals of their new research that mice which can be overweight from consuming an excessive amount of fats expertise adjustments that favor the creation of the premetastatic area of interest, on this case within the lungs. Particularly, platelet activation and blood clotting capability are elevated; as well as, fibronectin, the protein that connects lung tissue cells, is activated.
A platelet armor
It’s a longtime undeniable fact that weight problems promotes blood clotting, a course of that depends upon blood cells known as platelets. Certainly, as CNIO researcher and first creator of the research Marta Hergueta noticed, in animals fed with excessive fats, the cells which can be shed from the first tumor are surrounded, throughout their journey by the blood, by extra platelets than in mice with a traditional weight-reduction plan.
One speculation is that the platelets could possibly be making it troublesome for the physique’s defenses to detect the most cancers cells: the platelets would type “an armor around the tumor cells, preventing the immune system from recognizing and eliminating them,” explains Peinado.
Fertile breeding floor for metastasis
Along with affecting platelets, the CNIO group discovered that the high-fat weight-reduction plan will increase the expression of the protein fibronectin within the lung tissue the place tumor cells metastasize.
Fibronectin builds the tissue that connects lung cells, thus facilitating the creation of the premetastatic area of interest that hosts the tumor cell. It additionally allows the tumor cell to work together extra effectively with platelets. “We have seen that the interaction of the tumor cell with both the lung endothelium and the platelet is regulated by fibronectin,” says Peinado.
To check the implications of those outcomes for human sufferers, the CNIO’s Breast Most cancers Scientific Analysis Unit, directed by Miguel Ángel Quintela, participated within the research.
After analyzing blood samples from triple-negative breast most cancers sufferers, obtained earlier than surgical procedure and after present process chemotherapy, it couldn’t be verified that weight problems posed a further threat for the era of metastases. Nevertheless, sufferers with elevated blood coagulation—with a shorter prothrombin time—had been discovered to have the next threat of relapse at 5 years.
These findings “could help identify additional risk factors in breast cancer patients undergoing treatment, thus contributing to a better clinical management of the disease,” says Peinado.
Potential scientific utility
The work, carried out in collaboration with different CNIO models and different facilities in Spain and Canada, has explored preliminary avenues for scientific utility of the outcomes. Considered one of them was to switch the weight-reduction plan in animal fashions. When the high-fat weight-reduction plan was withdrawn, and the mice misplaced weight, platelet and coagulation conduct returned to regular ranges. Because of this, metastases had been decreased.
“I think these results, coupled with clinical studies from other groups, present a future where dietary intervention or dietary changes, along with control of platelet activity, may increase the efficiency of certain antitumor treatments,” Peinado says. “They are not going to be treatments by themselves, but they can complement them.”
Extra info:
The affect of a excessive fats weight-reduction plan and platelet activation on pre-metastatic area of interest formation, Nature Communications (2025). DOI: 10.1038/s41467-025-57938-9
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The Spanish Nationwide Most cancers Analysis Centre
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Excessive-fat weight-reduction plan promotes breast most cancers metastasis in animal fashions (2025, April 2)
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