The cells inside a tumour differ a lot.

While some remain "good" and do not cause trouble, others become aggressive, spreading to other organ sites, and it is very hard to predict which cells become aggressive or not.

Nevertheless, by isolating these aggressive cancer cells in in vivo tests on animals, researchers at The Rockefeller University and the Department of Biomedicine at the University of Bergen (UiB) have discovered a certain protein (PITPNC1) that characterise aggressive cancer cells.

"We discovered that the aggressive cancer cells that are spreading in colon, breast, and skin cancer contained a much higher portion of the protein PITPNC1, than the non-aggressive cancer cells," says researcher Nils Halberg of the CELLNET Group at the Department of Biomedicine at UiB.

"This means we can predict which of the cancer cells are getting aggressive and spread, at a much earlier stage than today."

The researcher also discovered that this protein, that characterizes the aggressive cancer cells, has got a very specific function in the process of spreading cancer.

The cancer cells spread from one place in the body to another, through the blood vessel.

To get into the blood vessels, the cell needs to penetrate tissue, both when it leaves the tumour and when it is attaching to a new organ.

"The protein PITPNC1 regulates a process whereby the cancer cells are secreting molecules, which cut through a network of proteins outside the cells, like scissors. The cancer cell is then able to penetrate the tissue and set up a colonies at new organ sites," Halberg explains.

His work reveals that PITPNC1 promotes malignant secretion by binding PI4P within the Golgi compartment of the cell, and begins localising RAB1B to the Golgi. 

RAB1B localization to the Golgi in turn recruits GOLPH3, which facilitates Golgi extension and enhanced vesicular release.

As a result, PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA and ADAM10.

In summary, PITPNC1 works as a PI4P-binding protein that enhances vesicular secretion capacity in malignancy.

Guided by the new discoveries, supported by the Bergen Research Foundation´s (BFS) Recruitment Programme, Halberg hopes to contribute to a better treatment of cancer patients.

"If we get to the point where we can offer a custom-made therapy that targets the function of this protein, we might be able to stop it spreading," says Nils Halberg. 

Source: Cancer Cell