Scientists at Mount Sinai Hospital in New York (USA) have solved an important mystery in cancer research : how malignant cells leave a tumor and travel to other parts of the body remain inactive for years, before causing a metastasis .
According to the study, published in the journal Nature Cancer , cancer cells remain dormant by secreting a type of collagen – called type III collagen [ 19459005] – in the environment around them, and they only become malignant when the level of this protein decreases. The researchers found that by enriching the cells’ environment with this type of collagen, they could force them to maintain the latent state and prevent the tumor from reappearing.
Cancer cells remain inactive by secreting a type of collagen into the environment around them and become malignant when the level decreases
“Our findings have potential clinical implications and may represent a novel biomarker to predict tumor recurrences –when the cancer reappears after a period during which it could not be detected–, as well as in a therapeutic intervention to reduce this recurrence ”, states José Javier Bravo-Cordero , professor at the Tisch Cancer Institute of Mount Sinai .
“This intervention aimed at preventing the awakening of dormant cells has been suggested as a therapeutic strategy to prevent metastatic growth,” he adds.
Better understanding of the biology of tumor latency and the development of new specific drugs could pave the way to cancer remission. “A combination of treatments that induce this latent state and therapies that specifically target these dormant cells would prevent local recurrence and metastasis,” adds the expert.
Tumor latency and collagen
Most cancer deaths are due to metastases, which can occur several years after tumor removal . Previous research has studied how scattered tumor cells come out of their dormant state. This new work, by contrast, shows how cells remain dormant.
To do this, the study used high-resolution imaging techniques, including intravital two-photon microscopy – a technology that enables latent cells to be viewed in their environment in real time in an animal alive-. This allowed experts to screen latent breast and head and neck cancer tumor cells in mouse models.
Scientists demonstrated that collagen abundance could be used as a potential measure to predict tumor recurrence and metastasis
Furthermore, thanks to this technology, it was possible to visualize the changes in the architecture of the extracellular matrix as tumor cells became dormant and how it changed when they woke up.
In patient samples, scientists demonstrated that collagen abundance could be used as a potential measure to predict tumor recurrence and metastasis. In mouse models, when researchers increased the amount of type III collagen around cancer cells that had emerged from a tumor, cancer progression was halted and the disseminated cells were forced into a dormant state.
Thus, this study suggests that metastasis could be prevented by using strategies aimed at enriching the tumor microenvironment in type III collagen, since the latency of tumor cells would be activated .
Di Martino et al. “A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy.” Nature Cancer 2021. DOI 10.1038 / s43018-021-00291-9
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