Researchers at Okayama University have recently published a study in Cells in which they reduced the size of oral cancer tumours by damaging the blood vessels surrounding the tumour cells.

Cancer cells have ingenious mechanisms of survival within the body.

One strategy they adopt is developing a network of blood vessels around themselves as a source of blood supply.

Scientists have long been investigating ways to prevent this blood flow to cancer cells.

CXCR4 is a protein known to be closely involved with tumour growth.

However, its exact role in tumour progression is unclear.

A research team led by Assistant Professor KAWAI Hotaka and YOSHIDA Saori(graduate student, D.D.S.), Assistant Professor EGUCHI Takanori at Okayama University has now shown that CXCR4 is the main culprit maintaining the arrangement of tumour blood vessels.

Firstly they found, immunohistochemistry on human clinical specimens revealed that tumour vessels expressed CXCR4 in human oral cancer specimens.

The next question to arise was whether the CXCR4-rich blood vessels were promoting tumour growth. In order to investigate this further, the oral cancer cells were transplanted into mice.

Once the tumour grew in mice body, they were given AMD3100 — a drug that antagonises CXCR4.

When the tumours were subsequently observed under a microscope, several areas were found to necrotic.

A characteristic pattern of necrosis was observed in which the tumour tissue that were at a distance away from the blood vessel was necrotic, leaving the tumour tissue close to the periphery of the blood vessel.

This randomised pattern of tumour cell death was termed ‘ tumour angiogenic inhibition triggered necrosis’ (TAITN) by the researchers.

The wide area of tumour tissue also showed a severe lack of oxygen which was accompanied by an impairment of angiogenesis.

CXCR4 inhibition thus seemed to induce tumour necrosis by damaging the blood vessels and preventing the cells of a healthy oxygen supply.

This study is the first to show the role of CXCR4 in promoting tumour growth by supplying cancer cells with a healthy, organised network of blood vessels.

Strategies that can disrupt this network can be explored further as anti-cancer therapies.

“CXCR4 plays a crucial role in tumour angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment,” concluded the team.

Background

CXCR4 is a protein vital in maintaining and growing the cells that produce blood within our body.

In foetuses, CXCR4 is also responsible for the formation of certain blood vessels. 

Incidentally, CXCR4 is also present in various forms of cancers such as breast, liver, and oral cancer.

Often, tumours which show the presence of CXCR4 tend to grow faster that those without.

Given its link with blood vessels and cancer progression, the research team from Okayama University sought out to investigate whether CXCR4 directly promotes cancer growth by supplying tumours with blood.

Source: Okayama University