The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis

Abstract

The glycoprotein (GP) Ib-IX complex is a platelet receptor that mediates the initial interaction with subendothelial von Willebrand factor (VWF) causing platelet arrest at sites of vascular injury even under conditions of high shear. GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder. Although knowledge on GPIb-IX structure, its basic functions, ligands, and intracellular signaling cascades have been well established, several advances in GPIb-IX biology have been made in the recent years. Thus, two mechanosensitive domains and a trigger sequence in GPIb were characterized and its role as a thrombin receptor was deciphered. Furthermore, it became clear that GPIb-IX is involved in the regulation of platelet production, clearance and thrombopoietin secretion. GPIb is deemed to contribute to liver cancer development and metastasis. This review recapitulates these novel findings highlighting GPIb-IX in its multiple functions as a key for immune regulation, host defense, and liver cancer development.

Relation of Mean Platelet Volume (MPV) with Cancer: A Systematic Review with a Focus on Disease Outcome on Twelve Types of Cancer

“…Moreover, activated platelets can facilitate tumor cell extravasation after the extracellular matrix degradation by matrix metalloproteinase-2 (MMP-2) [ 114 ]. Regarding the GPIba, GPIbα-mediated platelet adhesion to angiogenic vessels enhances angiogenesis and prevents hemorrhage from newly formed vessels contributing to cancer development and aggressiveness [ 115 ].…”

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

“…The GPIb-IX-V complex is one of the most abundant adhesion receptors exclusively expressed on megakaryocytes and platelets. GPIb-IX-V is involved in several physiological and pathophysiological processes, such as the unique ability to mediate the initial steps of platelet adhesion to injured vessel cells and the recruitment of inflammatory monocytes [ 21 , 22 ]. GPIbα is the key domain of this receptor complex because it contains both the vWF and the thrombin binding site and is, therefore, critically involved in hemostasis and thrombus formation [ 7 ].…”

Understanding organotropism in cancer metastasis using microphysiological systems

“…53,54 Once in the bloodstream, cancer cells confront challenges such as immune surveillance, shear forces, and interactions with platelets. [55][56][57][58] Microfluidic chips have dissected the biomechanical factors influencing circulating tumor cell adhesion, unveiling scenarios where adhesion is more likely in vessels experiencing vascular glycocalyx shedding or hemodynamic disturbances. 59 Surviving these challenges shapes subsequent metastatic steps, and microfluidic devices provide a tool to quantitatively measure endothelial barrier development and permeability.…”