P-Selectin – Cellular Glue

P-selectinI thought I’d make a switch to some biochemistry today. I was reading a few papers about the effects of platelets and platelet adhesion on cancer dissemination (not going to lie, I looked up the meaning of dissemination, especially pertaining to cancer, and it means the act of spreading widely). In a few of the papers I read the term “p-selectin” kept appearing. I had a brief understanding of p-selectin but upon looking up some more info on it, p-selectin is pretty cool.

P-selectin is quite literally an adhesive molecule for cells; that’s right, it’s cellular glue! Cell adhesion molecules, or CAMs, are proteins that provide the function of cell-cell or cell-extracellular matrix adhesion. How do these types of proteins act as glue? I haven’t had time to research it more, but it looks as though both physical interactions (think of Velcro) and charge interactions are responsible for the “stickiness.”

P-selectin proteins in particular spring into action on activated endothelial cells and activated platelets. Endothelial cells are found on the inside walls of blood vessels, and therefore p-selectin is an important protein involved in platelet aggregation, especially at the sites of injury. It helps your blood clot!


P-selectin has been a common suspect for promoting the metasis, or spreading of cancerous cells from one organ to a non-adjacent site, of some cancer cells. P-selectin can aid in the adhesion of certain cancer cells to platelets which, when combined with certain growth factors, may help the cancerous cells spread. I briefly read that the drug heparin indirectly inhibits the activity of p-selectin since heparin halts an endoglycosidase from degrading heparin sulfate. I found a few papers that reported the binding of p-selectin may be a sulfidation dependent process. Therefore blocking the degradation of heparin sulfate means that sulfidation will not occur and p-selectin can’t spring into action.

Of course if, among other actions, heparin blocks the action of p-selectin that means platelet aggregation may not occur at sites of injury. Talk about a bad day if your p-selectin isn’t working. It could lead to uncontrollable bleeding even with the smallest puncture of a blood vessel.

It would be really interesting to see if more research comes out about p-selectin. It seems like a good candidate for some bioengineering, possibly the key to halting the spread of certain cancers. Imagine if one small molecule could save people from poor health and suffering?

Sources:
Thanks to Google! for defining “dissemination”

What got me interested in finding out more:
McCarty OJ, Mousa SA, Bray PF, Konstantopoulos K. Immobilized platelets support human colon carcinoma cell tethering, rolling and firm adhesion under dynamic flow conditions. Blood 2000 Sep; 96(5): 1789-1797.

Hughes AD, Mattison J, Western LT, Powderly JD, Greene BT, King MR. Microtube device for selectin-mediated capture of viable circulating tumor cells from blood. Clin Chem 2012:58:846–53

Info on p-selectin:
Disdier M, Morrissey JH, Fugate RD, Bainton DF, McEver RP (March 1992). “Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway”. Mol. Biol. Cell 3 (3): 309–21. PMC 275532. PMID 1378326.

Info on p-selectin in terms of cancer metasis:
Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A (March 2001). “Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis”. Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3352–7. doi:10.1073/pnas.061615598. PMC 30657. PMID 11248082

Heparin info: Bar-Ner M, Eldor A, Wasserman L, Matzner Y, Cohen IR, Fuks Z, Vlodavsky I (August 1987). “Inhibition of heparanase-mediated degradation of extracellular matrix heparan sulfate by non-anticoagulant heparin species”. Blood 70 (2): 551–7. PMID 2955820

Of course, the Wikipedia page on p-selectin is always a great resource

[Image Credit] Neveu, Curtis, Wikimedia Commons

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