Monday, February 21, 2011

Calreticulin, CD47 and Cancer

Cancer is a subject that has always baffled me, and I'm sure I'm not the only one. We recently discussed a paper in the RSP Journal Club about how our immune system tried to fight cancer and it's one discussion I truly regret missing. Surprisingly enough, the paper made enough sense to me while I was going through it on my own, and in this post, I'll try to present to you the information I could make sense of (forgive me for not going into the details of the 'methods' section- I'll probably confuse myself if I even tried right now. In any case, the results take the cake this time!)

So this paper studied the effects of Calreticulin (CRT) and CD47 (Cluster of Differentiation-47) and in cancer cells. I vaguely remembered learning about CRT in high school, but had to googled its exact function for the purpose of understanding this paper. So CRT is a protein found in the endoplasmic reticulum (ER). It binds to distorted proteins and stops them from leaving the ER.

So what CRT does is sends a signal to the immune system, which helps the immune system detect and destroy foreign particles through a process known as 'phagocytosis', which is basically how a cell 'eats' (fun fact of the day: 'pinocytosis' is how a cell 'drinks', i.e. engulfs a liquid particle).

What this study discovered was that cancer cells, in fact, express CRT to a large extent, certainly more than normal cells do (these are called pro-phagocytic signal). In doing so, they're, in a way, sowing the seeds for their own destruction.

Why, then does our immune system not destroy cancer cells? What prevents these cancer cells from being 'eaten'?

The answer to that is a protein known as CD47, which gives anti-phagocytic signals to the immune system, counterbalancing the pro-phagocytic signals that the immune system receives from CRT. These signals are also produced by the cancer cells in large amounts, which helps the cancer cells serve their best interests.

So the next step in this study, I suppose, is to look for a way to block the expression of CD47. However, this is more complicated than it sounds, because CD47 expression must be blocked only in cancer cells, and CRT growth must also be regulated, to ensure that normal cells are not being destroyed by the immune system.

It seems strange to me that cancer cells would produce CRT, which could destroy them and then produce CD47 to counterbalance CD47 when their job would be made much easier by not producing the former at all. But then, if CRT wasn't produced by them, would our immune system have come up with a way to fight the cancer? I guess cancer research always raises as many questions as it answers.


Link to paper: I'm sorry, but only the abstract is available for free. Here's the link to that: http://stm.sciencemag.org/content/2/63/63ra94.abstract

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