The vast majority of deaths from cancer are due to secondary tumors, about 90% of them. Secondary tumors are those from a metastasized cancer; one that has spread to other parts of the body – a tumor that is not in the original tumor site. For cancer cells to break free from the original tumor, they need a bit of help from other cells around them.

Experts have believed that several types of cells in the original tumor’s environment play a role in helping the cancer cell break free and spread to other parts of the body. They suggested that immune system cells and those that form connective tissue are involved.

Platelets, the blood cells involved in coagulation of blood (clotting), are also involved, say scientists from MIT (Massachusetts Institute of Technology). Before this latest study, nobody knew what the exact role of platelets were in helping cancer cells metastasize.

Richard Hynes, the Daniel K. Ludwig Professor for Cancer Research, and team explain that platelets release chemical signals that make cancer cells become more invasive and establish themselves in new locations.

Their study is published in this week’s edition of Cancer Cell. The authors explain that their findings may pave the way for research into new medications that could undermine a cancer cell’s ability to spread. They emphasize that these new drugs, if they are created, would only work on patients before metastasis occurred.

Cancer biologists have long thought that platelets help cancer cells clump together, making it easier for them to get stuck in new locations – thus promoting metastasis. However, a number of researchers wondered whether platelets might not have a more active role. Platelets contain several growth factors and cytokines, a number of which can trigger cancerous growth.

Most cancer cells undergo EMT (epithelial-mesenchymal transition) before they are able to metastasize – this is a kind of shift. Cells lose their ability to adhere to each other and start to drift from their original sites.

Lead author, Myriam Labelle, said that she discovered that if grown in contact with platelets in a lab dish, cancer cells would undergo EMT. She also discovered that TGF-beta, or TGF-b (transforming growth factor beta), types of genes, were very active. They already knew that TGF-beta promotes EMT.

By depleting the in vivo platelets of TGF-beta, Labelle found that metastasis was blocked.

Labelle also found that when exposed just to TGF-beta, they would not become metastatic. This means there must be an extra signal coming from the platelets.

Hynes explained that:

“(platelets are) little bags of stickiness and
growth factors.”

Platelets are designed to facilitate wound healing; they release many chemicals, apart from TGF-beta. The problem is that none of these additional chemicals have been found to trigger metastasis.

The researchers found that for cancer cells to spread, to become metastatic, they needed to have direct physical contact with platelets. When these two come into contact, they activate the NF-kappa-b pathway, which regulates immune response to infection. For the switch to occur – for the cell to turn from a localized one to a metastasized one – both signals, NF-kappa-b activation and TGF-beta are necessary.

Cells get the initial stimulus to start spreading while they are still in their original site. The scientists suspected that they get an additional stimulus when they enter the bloodstream; a boost that makes it easier for them to cross the blood vessel walls into a new tumor site.

Blood cells may also promote metastasis, the scientists suspect. Labelle is currently carrying out experiments to find out what the role of blood cells might be, and how they work in combination with platelets. She is also trying to find out how platelets activate the NF-kappa-b pathway in cancer cells.

When scientists can understand properly which signals are required for a cancer cell to become metastatic, research into new medications that can prevent metastasis can occur.

Labelle said:

“It’s important to understand exactly what platelets are doing, and eventually this could be an opportunity for drugs that would treat metastasis.”

The new drugs would probably be effective in stopping primary tumors from spreading, but would most likely not be effective for secondary tumors that had already formed and established themselves.

Written by Christian Nordqvist