Cancer Studies Oxygen deficiency causes cancerous tumors to metastasize

Cancer Studies Oxygen deficiency causes cancerous tumors to metastasize / Health News
When there is a lack of oxygen, cancer tends to spread
In their current investigations, scientists from the Ludwig Maximillians University (LMU) in Munich were able to decipher the mechanism that causes tumors at low oxygen concentrations to intensify their scattering into other tissues. The researchers observed that when oxygen deficient, a small molecule is slowed down, which normally initiates a protective mechanism.


The research team led by Professor Heiko Hermeking was the first to determine the mechanisms responsible for the fact that tumors are prone to increased metastasis at low oxygen concentrations, the LMU reports. The effect is important in many cancer patients, as tumors are often poorly perfused and therefore often have a poor oxygen supply, the scientists report. Due to this lack of oxygen, the tumors respond badly to radiation and chemotherapy and are prone to metastasis, the experts explain the connection. The scientists have published the results of their latest study in the journal "Gastroenterology".

In cancer, oxygen deficiency in the tissue leads to increased metastasis of the tumors. (Image: Juan Gärtner / fotolia.com)

Special RNA molecule increasingly disabled
In their studies on colorectal carcinoma, the scientists found that in more than half of the tumors the so-called "tumor suppressor p53" was inactivated. In earlier studies, Prof. Hermeking had already demonstrated that this gene encoded a protein which, in turn, directly induces an extremely short RNA molecule - the so-called micro-RNA-34a (miR-34a). This in turn plays a central role in tumor suppression. "In intestinal carcinomas, we have observed that miR-34a is inactivated particularly frequently in metastatic tumors, where oxygen deficiency often occurs," reports Prof. Hermeking from the results of the study.

Link between metastasis and lack of oxygen decrypted
The inactivation of miR-34a was the first time scientists were able to directly relate to the lack of oxygen. "At low oxygen levels, the tumor cells produce the so-called hypoxia-induced factor HIF1a, which directly inhibits the protective RNA molecule," reports LMU. In addition, a reaction chain is set in motion, which in its course upregulates other proteins and ultimately initiates a process in which locally growing, non-invasive surface cells transform into aggressive cells. These invade other tissues and the tumor metastasizes. The process is referred to as epithelial-mesenchymal transition (EMT) and also play an important role in the migration of cells during embryonic development.

Special protein with far-reaching effects
According to the researchers, the protein PPP1R11 is involved in the disastrous reaction chain. The production of this protein was particularly high on the invasion front of poorly oxygenated tumors. Normally, the production of PPP1R11 in the cells is suppressed directly by miR-34a and thus indirectly also by the tumor suppressor p53. In this way, the reaction chain can, as it were, be reversed and a protective mechanism triggered, which keeps the cells in place. This inhibits metastasis.

New approaches to therapies
According to the researchers, the new study results also indicate that metastatic intestinal tumors could possibly be treatable if important proteins of the indicated reaction chain could be inhibited and parallel activation of miR-34a could be achieved. "In particular, molecules that could substitute miR-34a and take over their function are currently being investigated in clinical trials," explains Prof. Hermeking. Especially for tumors with poor oxygen supply, these could be of high relevance for future treatment options, the study authors conclude.