CD44 antigen is a cell surface glycoprotein expressed on a large number of cell types [including cancer stem cells] involved in cell-cell interactions, cell adhesion and migration. CD44 is involved in a wide variety of cellular functions, including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. CD44 is a receptor for hyaluronic acid and internalizes metals bound to hyaluronic acid (HA) , and can interact with other ligands, such as osteopontin (OPN), collagens and MMPs.

Transcription of the CD44 gene is at least partially activated by beta-catenin and Wnt signaling (also linked to tumor growth). CD44 is involved in cell proliferation, cell migration, angiogenesis, the presentation of cytokines, chemokines and growth factors incorresponding receptors and in cell survival.

All these biological properties are necessary, but they are also associated with pathological activities of cancer cells. High levels of the adhesion molecule CD44 on leukemic cells are necessary for the development of leukemia. In many cancers (kidney and non-Hodgkin’s lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome.

Variations in CD44 are reported as cell surface markers for breast and prostate cancer stem cells, but also found as a marker of increased survival in patients with epithelial ovarian cancer CD44 interacts with: Epidermal growth factor receptor (dependent on hyaluronan), Fibrin [immobilized] fibrinogen, Osteopontin, etc.

The main ligand of CD44, hyaluronan, activates it resulting in the activation of cell signaling pathways that induce the proliferation of

cells, increase cell survival and enhance cell motility. CD44 plays a role in regulating EMT and tumorigenesis, CD44 is a marker of CSCs in many tumor types [Cell Mol Life Sci.2021]. Apart from the typical CD44 isoform (CD44s), CD44v is also distinguished where the CD44v /CD44s switch plays a decisive role in tumor progression.

Interaction of isoforms with HA, OPN and MMPs, leads to cancer-related signaling. Mechanism of action of CD44 in relation to TGF-β1 and its connection with EMT in human prostate cancer cells revealed.

Surface expression of CD44 activates MMP-9 and their secretion is regulated by OPN. MMPs are involved in bone resorption and tumor progression, while in many tumor cells, MMPs and CD44 are highly expressed and correlated with invasiveness and metastasis.

MMPs play a role in tissue remodeling [growth], bone resorption, wound healing, and angiogenesis. CD44 binds to MMP-9 on the surface of murine mammary carcinoma and human melanoma cells and anchors MMP-9 to the surface of the cell.

ΝΟΤΕ: For doctors or hospitals that are interested in researching CD44, the research center can set this antigen with flow cytometry.

SOURCE: Molecular Cancer 2007