Thursday, 31 January 2013

Breast cancer cells TWIST macrophages to aid blood vessel growth

Epithelial to mesenchymal transition (EMT) is a process where epithelial cells, those that form tissues of our major organs such as the lungs, gut, skin and breast can transform into mesenchymal cells. This transition causes the cells to take on a more motile and flexible pattern of behaviour. EMT is a crucial process in the initial development of the human body and also helps to repair damaged tissue following wounds. However, cancer cells are also able to exploit the process of EMT to help them to help them leave the mass of epithelial cells forming the primary tumour and move to distant secondary sites.

The processes that regulate EMT during development are highly regulated, this is achieved in part by small proteins called transcription factors. Transcription factors interact with DNA and recruit machinery that controls when genes are made into the proteins, which ultimately bring about changes within the cell. Three transcription factors particularly important in EMT during development are: Slug, Snail and Twist; recently these proteins have begun to be investigated in the context of cancer. They are often up-regulated in cancer and their presence in tumours may indicate a poor survival rate for patients. They promote cancer mainly through their effects on proteins involved in EMT, and much research is being currently undertaken with this aspect in mind.

However, a study published this month in the journal Cancer Research by Low-Marchelli and colleagues describes a novel function for Twist in the way in which cancer cells recruit blood vessels. This process, termed angiogenesis, is required to give a tumour sufficient blood to continue to grow. Normal breast epithelial cells do not express detectable levels of Twist, but when Twist is artificially added to these cells they are better at encouraging blood vessel growth.

While looking for the mechanism by which Twist increases angiogenesis, the group found that Twist expressing breast cells released more of one particular signalling protein, CCL2, than normal breast cells. This CCL2 was shown to be required for the promotion of blood vessel growth by Twist; interestingly this was independent of Twist’s role in EMT. CCL2 belongs to a group of proteins called chemokines which act to attract other cells to move towards their source, in this case the breast cancer cells. The cells which are attracted to this CCL2 are an immune cell called macrophages, cells which are normally required for the removal of damaged, infected or even cancerous cells. However, the signalling molecules released by macrophages can also promote tumour growth directly as well as promoting stages of blood vessel development.

In conclusion, this study has elegantly revealed a mechanism where Twist in breast cancer cells can cause increased CCL2 levels to attract macrophages and promote blood vessel growth. This is an interesting new facet to Twist biology, adding further complexity to its role in cancer.

Mentioned Articles

Low-Marchelli JM, Ardi VC, Vizcarra EA, van Rooijen N, Quigley JP, Yang J. (2013)
Twist1 Induces CCL2 and Recruits Macrophages to Promote Angiogenesis
Cancer Res. 2013 Jan 15;73(2):662-71. doi: 10.1158/0008-5472.CAN-12-0653.

Shioiri M, Shida T, Koda K, Oda K, Seike K, Nishimura M, Takano S, Miyazaki M. (2006)
Br J Cancer. 2006 Jun 19;94(12):1816-22. doi:10.1038/sj.bjc.6603193

J Exp Clin Cancer Res. 2010 Sep 1;29:119. doi: 10.1186/1756-9966-29-119.

No comments:

Post a Comment