CD31: A Comprehensive Look at an Essential Biomarker

CD31, also known as PECAM-1, was originally described as a cell surface antigen present on platelets and megakaryocytes. CD31 is a member of transmembrane glycoproteins expressed on cells of all lineages within the vascular system. CD31 antigen belongs to PECAM proteins that are now recognized as belonging to the immunoglobulin superfamily because they contain large numbers of extracellular immunoglobulin domains with conserved C2-type calcium binding sites.

CD31 is expressed on CD34+ hematopoietic stem cells, CD14+ monocytes and CD16+ NK cells in humans. CD31 is present on platelets at their proplatelet extensions. CD31 has also been reported to be expressed on endothelial smooth muscle cells but not on cardiac myocytes.

CD31 has been shown to bind thrombospondin-1 (TSP1), CD41a CD36, CD24 and neural cell adhesion molecules (NCAM). CD31 also binds directly to fibrinogen or indirectly through thrombospondin 1 (TSP1).

CD31 acts as an adhesion molecule that facilitates leukocyte migration to sites of infection or tissue damage by binding intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. CD31 also functions in concert with LFA-3 and Mac-1 in order to facilitate CD14+ monocyte migration. CD31 functions in CD34+ hematopoietic stem cells by regulating CD34+ CD42a interactions during adhesion and trans endothelial migration. CD31 also functions as a cell surface calcium ion pump that controls the distribution of calcium into and out of intracellular stores in platelets.

CD31 is an established biomarker for angiogenesis during vascularization. CD31 is believed to play an important role in cancer metastasis due to its ability to support dynamic multi-directional interactions with other proteins on both endothelial cells and platelets. CD31 is also involved in thrombus formation when bound with fibrinogen or TSP1.

CD31 has been used as a cancer biomarker due to its increased expression in various cancers including myeloid malignancies. CD31 plays an important role in tumor angiogenesis. CD31 expression can be used to discriminate between malignant and benign oral tumors. CD31 may be a useful predictor of metastatic disease in lung cancer. Patients with CD31+ diffuse large B-cell lymphoma (DLBCL) had poorer outcomes than CD31- cases. CD31 has been used as a prognostic marker in different types of cancer such as gastric, hepatocellular carcinoma and renal cell carcinoma.

CD31 can be an additional predictor for metastatic relapse after transarterial chemoembolization (TACE) as part of the treatment regimen for hepatocellular carcinoma (HCC). CD31 expression is associated with poor prognosis, according to a meta-analysis studying CD31 expression in colorectal cancer. A study looking at CD31 expression on inflammatory myofibroblastic tumor cells suggests its use as a potential diagnostic marker. CD31 expression is associated with poor prognosis, according to a meta-analysis studying myeloid CD31+ cells in myeloproliferative neoplasms.

CD31 is a promising therapeutic target in cancer. Antibodies against CD31 can be used to deplete CD31+ cells. CD31 has been shown to interact with anti-cancer drugs such as elesclomol, mocetinostat and the CDK inhibitor roscovitine.

Anti-CD31 monoclonal antibodies have been used for CD31-targeted therapy of myeloid malignancies and CD31 siRNA treatment. CD31 has also been used as an immune checkpoint inhibitor target for solid tumors, due to its role in inflammation, angiogenesis and metastasis.