I 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?
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