Note in Science page
Created Jan 02 11, Updated Jan 02 11 23:34
Calreticulin: an "eat me" signal in cancer cells go to comments

Researchers at the Stanford University School of Medicine have identified calreticulin (CRT) as the pro-phagocytic (“eat me”) signal that is highly expressed on the surface of several human cancers, but was minimally expressed on most normal cells.
They’ve also shown that this signal should be counterbalanced by the expression of an anti-phagocytic (“don’t eat me”) signal identified as CD47 in order for the (CRT positive) cancer cells to survive.


Calreticulin (pdb 1hhn) skeleton structure © wikipedia.org

CD47 is a cell surface protein that serves as a signal inhibiting phagocytosis through ligation to its receptor SIRPα (signal regulatory protein &alpha) on phagocytic cells.
Blocking CD47-SIRPα interaction with a monoclonal antibody against CD47 results in phagocytosis of cancer cells and leads to in vivo tumor elimination! Yet normal cells remain mostly unaffected as they don’t display the “eat me” signal (Cell surface CRT is expressed on cancer, but not most normal, stem and progenitor cells).

The researchers also found that the most aggressive cancers were the ones making the most CRT: CRT expression is associated with tumor progression and worse clinical outcome across several tumor types. This raises hopes that some of aggressive cancer cells may be the most vulnerable to therapies targeting CD47 and CRT.

If all (aggressive) cancer cells have to make CRT (conferring them some survival advantage!?) then just blocking the counterbalancing signal CD47 would make a very promising, ~simple and ~side effect free therapy! (but it’s more likely that there will be selection for mutant cancer cells that can thrive without CRT but at least it’s another weapon against cancer)

Science Daily article
Science Translational Medicine article


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