Tumor hypoxia promotes metastasis

Metastases are formed by cancer cells that leave the primary tumor. A research group at the University of Basel has now identified a lack of oxygen as a trigger for this process. The results reveal an important relationship between oxygen supply to the tumor and the formation of metastases. This study may open up new treatment strategies for cancer.

Once the tumor has metastasized, the chances of recovery are significantly reduced. Previous studies have shown that metastases are formed by clusters cancer cell It separates from the primary tumor and travels to new tissue through the bloodstream. However, so far little is known about why these clusters of circulating tumor cells (CTCs) leave tumors first.

Lack of oxygen leads to more metastases

The research group of Professor Nicola Aceto of the Department of Biomedical Sciences at the University of Basel Lack of oxygen Involved in the isolation of CTC clusters from tumors. This is an important starting point for the development of new cancer treatments.

A mouse model of breast cancer formed the basis of the experiment. Researchers Oxygen supply Inside these tumors, CTC exfoliation and biological properties of their molecules and cells are comparable to those of human cancer tissue.

Different levels of different areas of the tumor oxygen: Oxygen-deficient cancer cells were found in relatively few tumor vessels or in well-defined peripheral areas of the tumor. Next, the team investigated CTC clusters isolated from these tumors and found that they also suffered from anoxia. This led to the conclusion that cells will leave the tumor if they do not receive enough oxygen. “It looks like people are crowded in a small space. Some people go out to find fresh air,” Aceto says.

Further experimentation has shown that these oxygen-deficient CTC clusters are particularly dangerous. Metastases formed faster and survival time in mice was reduced compared to normal oxygen content clusters. “If your tumors don’t have enough oxygen, those CTC clusters that are especially likely to metastasize will drop out,” Aceto says.

Stimulating angiogenesis as a therapeutic approach

This insight has led researchers to scrutinize the effects of a treatment called a pro-angiogenic treatment. They stimulated the formation of blood vessels and promoted the supply of oxygen. Tumor cells.. As expected, the number of segregating CTC clusters was reduced, mice formed fewer metastases and they survived longer, but at the same time the size of the primary tumor increased significantly.

“This is a provocative result,” Aceto says. “If you give your tumor enough oxygen, cancer There is no reason for the cells to leave the tumor and metastasize. Meanwhile, this will accelerate the growth of Primary tumor“

The next challenge is to transfer these findings to the clinical setting. There, tumor characteristics vary from patient to patient. “But we are looking for substances that improve oxygen supply tumor Can inhibit the formation of metastases breast cancer, Alone or in combination with other drugs. “

This study Cell report..

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Nanomaterial-based strategies for the treatment of hypoxic tumors

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For more information:
Cell report (2020). DOI: 10.1016 / j.celrep.2020.108105

Provided by
Basel University

Quote: Tumors lacking oxygen promote metastases (September 8, 2020).

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