As cancer advances, metastases begin to form, which are extremely hard to stop. At this point, treatment strategy has to be altered and more aggressive medicine must be used. However, science does not have all the needed knowledge about what causes metastasis to develop better treatments to battle them at early stages or to prevent them in the first place. Now research at The Scripps Research Institute is aiming to explain mechanisms behind cancer me metastasis that make them so hard to stop.
The study revealed an additional mechanism, which explains how a molecule long linked to cancer progression appears to “seed” the body with metastatic cells long before doctors would typically detect a primary tumour. This molecule is called epidermal growth factor receptor. It encourages growth of blood vessels during the development of the tumour.
This feeds the primary tumour as well as provides paths for cancer cells to escape tumour and to migrate to other parts of the body. If cancer cells have more of epidermal growth factor receptor molecules, the cancer tumour consequently has more angiogenic blood vessels, which can be used for the cells to migrate in very early stages of cancer. This discovery challenges widespread belief that cancer metastases appear only in later stages – in fact tumours seed metastasis way earlier than doctors expect.
Previous study confirms these findings. It demonstrated that tumours with high levels of epidermal growth factor receptor molecules (EGFR) delivered from 10 to 100 times more cancer cells to secondary organs. Petra Minder, first author of the new study, said: “when we downregulated EGFR so it wasn’t expressed anymore, the tumour cells were not able to disseminate efficiently. This gave us a hint that EGFR plays a role in intravasation [an early step of metastatic dissemination during which tumour cells enter angiogenic blood vessels]—we were just not sure how.”
During the research, scientists experimented with chick embryos to see how important EGFR levels are in the cancer development. They found that that EGFR signalling starts a chain reaction inside tumour cells, which in the end results in the release of a molecule, called vascular endothelial growth factor (VEGF). This molecule is known to be active in almost all forms of solid tumours. When VEGF is released, it soon binds to endothelial cells, which induces growth of new blood capillaries and vessels within a developing tumour.
Vessels in small, developing tumours are not a new thing for science. In fact, scientists have been observing them for many years, but thought they only supply the tumour with oxygen and nutrients. Now scientists also know that these small blood vessels are also used for dissemination of tumour cells into the whole body. They are so useful for the spread of cancer because of their structure – they are dilated and unusually permeable, which allows tumour cells to slip into these vessels, escape the primary tumour site, and migrate through the body.
When these cells settle down in a new place, they grow very slowly, which makes it very hard to detect them. This is why metastases are usually detected only when primary tumour is diagnosed. EGFR-inhibiting drugs are already in use, but they had only limited success in treating human patients, because they only target effects of EGFR in primary tumour growth. These drugs do not address the role of EGFR in spreading the tumour cells.
This means that new drugs must be developed. Results of this research may be the beginning of the development of new therapies that would help fight metastases in early stages. However, it will take a lot of time till the results will reach practical applications in cancer therapies.