Metastasis Likely Caused by Lack of Oxygen in Cancerous Tumors, Study Shows

Metastatic cancer refers to cancer that has spread from its original location to other parts of the body. This process occurs when cancer cells break away from the original tumor and travel through the bloodstream or the lymphatic system to another area of the body. If the new location these cells take up residence in is a vital organ—such as the brain, liver, bones, or lungs—they can become deadly and very difficult to treat.

Circulating tumor cells (CTCs) have been shown to be the cause of metastasis, so if we could keep these cells from breaking off of the original tumor, we could keep metastasis from taking place and save lives. But how?

According to a new study from the University of Basel, a lack of oxygen may be causing the separation of CTC clusters from their tumors, resulting in metastasis.

Photo: Adobe Stock/Christoph Burgstedt

The study, called “Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells,” has been published in the journal Cell Reports. Nicola Aceto, PhD, Swiss National Science Foundation assistant professor and group leader of the Cancer Metastasis Lab at the University of Basel, led the study.

The team used a mouse model to analyze the oxygen supply inside of breast cancer tissues, the detachment of CTCs, and the molecular and biological properties of those CTCs. They found that different areas of the same tumor were supplied with different amounts of oxygen. Those cancer cells that were located in areas with the least oxygen were the most likely to break away.

“It’s as though too many people are crowded together in a small space,” explains Dr. Aceto. “A few will go outside to find some fresh air.”

Photo: Adobe Stock/crevis

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The team also learned that the CTC clusters with low oxygen supply (known as “hypoxia“) formed metastases faster and shortened the mice’s survival time more than the CTC clusters with normal oxygen content.

“In a tumor, hypoxia is generally expected to be confined to the core and within regions that are poorly vascularized. However, this is an apparent paradox in the context of metastasis biology because metastatic cancer cells need to have access to functional blood vessels to achieve dissemination. We thought of tackling this controversy by directly addressing the role of hypoxia in spontaneous metastasis models in vivo and in relation to CTC generation and metastasis,” the study says.

The researchers then created a simulated formation of blood vessels in order to boost the oxygen levels supplied to the tumor cells. As expected, increasing the oxygen supply caused fewer CTC clusters to break off, which resulted in fewer metastases and overall longer-living mice. However, the original tumor thrived with increased oxygen and grew more quickly.

Photo: Adobe Stock/romaset

“This is a provocative result,” says Aceto. “If we give the tumor enough oxygen, the cancer cells have no reason to leave the tumor and metastasize. On the other hand, this accelerates the growth of the primary tumor.”

The researchers look forward to applying their findings in a clinical setting to see how the characteristics of cancer vary from patient to patient. In the future, their research will hopefully be applied to treatment strategies to help improve the way we treat cancer.

“We speculate that therapies aimed at reducing intra-tumor hypoxia, alone or in combination with anticancer agents, may provide a new opportunity to blunt the metastatic spread of cancer in breast cancer patients,” the study concludes.

We can’t wait to see what happens next! This could be an absolute game-changer in the prevention of metastatic cancer!

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