CD44 Specific Neutra™ Antibody Products

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The CD44 molecule is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and migration. Widely expressed on many cell types, including immune cells, epithelial cells, and cancer cells, CD44 plays a key role in the regulation of the immune response and pathological states such as cancer metastasis. It primarily binds to hyaluronic acid, a major component of the extracellular matrix, but also interacts with other ligands, facilitating cell movement and activation. CD44 is significant in various cellular processes, including lymphocyte activation, recruitment to inflammation sites, and tumor cell proliferation and migration.

Its Gene ID: 960, UniProtKB ID: P16070, OMIM ID: 107269

The Structure of CD44

CD44 is a complex transmembrane glycoprotein that exists in multiple molecular forms, including the standard isoform CD44s and the variant isoform CD44v. CD44 is encoded by the CD44 gene located on the short arm of the Human chromosome 11, which consists of 19 exons. Specifically, the first 5 exons (exons 1-5) and the last 5 exons (exons 16-20) consistently encode CD44s, the most common and smallest CD44 protein with a molecular weight of about 85-95 kDa. CD44 is composed of three regions: the extracellular domain, the transmembrane region, and the intracellular tail. The CD44v isoforms contain additional proximal parts of the membrane coded by a combination of single variable exons or multiple variable exons.

Fig.1 Human CD44 gene. (Xu, Hanxiao, et al., 2020) Fig.1 Structure of CD44 gene.¹

Fig.2 Human CD44 Structure. (Xu, Hanxiao, et al., 2020) Fig.2 Structure of CD44 protein.¹

The Ligands of CD44

CD44 interacts with several ligands, most notably hyaluronic acid (HA), which is the primary constituent of the extracellular matrix and serves as CD44's most common ligand. Other significant ligands include osteopontin, fibronectin, serglycin, and chondroitin. These interactions facilitate various cellular functions such as adhesion, migration, and proliferation. HA binding to CD44 triggers signaling pathways important for cancer cell survival and metastasis, while osteopontin influences CD44-related cancer cell motility and survival through specific pathways.

Molecules that CD44 Regulates

CD44 regulates the expression and activity of matrix metalloproteinases (MMPs), particularly MMP9 and MMP2. This regulation can occur both in HA-dependent and HA-independent manners, facilitating tumor invasion and metastasis by degrading the extracellular matrix, which is essential for tumor cell migration and invasion.
CD44 influences the expression of cell cycle-related proteins such as cyclin D and cyclin A. Specifically, CD44 upregulates cyclin D1, enhancing the proliferation of gastric stem cells and promoting progression from the G1 phase to the S phase of the cell cycle, thus facilitating cell proliferation.
CD44 impacts β-catenin signaling by reducing its expression and increasing the phosphorylation of β-catenin, leading to decreased stability of the Wnt/β-catenin pathway. This modulation affects nuclear accumulation of β-catenin, crucial for regulating genes that drive cell migration and invasion.

Fig.3 Pathways that CD44 regulates. (Xu, Hanxiao, et al., 2020) Fig.3 Signaling pathways which CD44 regulates.¹

Roles of CD44 in Cancer Progression

Cancer Initiation: CD44 is crucial in cancer initiation by promoting epithelial-mesenchymal transition (EMT) and maintaining cancer stem cell properties, which are key for tumor cell migration, invasion, and resistance to therapy. These roles highlight CD44 as a target for therapeutic intervention and as a biomarker for cancer stem cells.
Tumor Development: During tumor development, CD44 modulates various signaling pathways, enhancing tumor cell proliferation, invasion, and metastasis. This involves interactions with various ECM components and activation of pathways like PI3K/Akt, influencing tumor behavior and progression.
Prognosis: CD44 serves as a prognostic marker in various cancers, with its expression often correlating with poor clinical outcomes. High levels of CD44 are associated with increased tumor aggression and decreased survival rates, making it a significant indicator of prognosis in cancer patients.

Creative Biolabs is dedicated to offering a complete range of CD44-related products and antibody solutions to further assist your exploration of CD44's extensive applicability and potential biological understanding. With our state-of-the-art neutralizing antibody and recombinant antibody technology platform, we are confident in supplying top-tier service. Our CD44 recombinant antibody product undergoes stringent quality control and performance validation, ensuring its reliability and efficiency in diverse biological research.

REFERENCE

Xu, Hanxiao, et al. "CD44 as a tumor biomarker and therapeutic target." Experimental Hematology & Oncology 9 (2020): 1-14.

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