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Cells secrete a type of collagen to remain inactive and wake up when collagen levels fall to create metastatic cancer. The cells remain quietly secreting a type of collagen type III, in the environment around them, and become malignant only when the collagen level decreases.

The researchers found that by enriching the environment around the cells with this collagen, they could force the cells to remain dormant and prevent the tumor from recurring. Tumor cells in a collagen I matrix with the cells could actively proliferate.

The findings could lead to a new biomarker for predicting tumor recurrence, as well as a therapeutic intervention to reduce local and distant recurrences. This intervention aimed at preventing the awakening of dormant cells has been proposed as a therapeutic strategy to prevent metastatic growth.

As the biology of tumor dormancy is revealed, new drugs [combination therapies] are being developed that dormant inactivated cells, ultimately preventing local recurrence and metastasis of the cancer. When the cells are in Collagen III, the other type of collagen then it triggers lethargy and the cells stop dividing and reshape the uterus around them.

Most cancer deaths are due to metastases, which can occur several years after a tumor is removed. Previous research had studied how scattered tumor cells emerge from dormancy. This new work showed how cells remain inactivated.

The study [using a two-photon endobiological microscopy technique] was able to image inactive cells in their environment in real time in an experimental animal [breast, head and neck cancer cell lines]. Using the technology, the researchers were able to visualize changes in the extracellular matrix architecture as the tumor cells became dormant and how they changed when they awoke.

In patient samples, the researchers showed that plenty of collagen could be used to predict tumor recurrence and metastasis. In the models, when the scientists increased the amount of type III collagen around the cancer cells that had left a tumor, the cancer progression stopped and the scattered cells were forced into an inactive state.

SOURCE: MOUNT SINAI SCHOOL OF MEDICINE [Nature Cancer Febr. 2022]