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Pgp-1
Pgp-1
Pgp-1(6)
CD44 is part of a family of matrix adhesion molecules, that bind hyaluronate, collagen, laminin, and fibronectin, and maintains polarization of epithelial cells, is involved in cell-cell interactions, cell adhesion, lymphocyte activation, recirculation, homing, hematopoiesis, tumor metastasis, cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, and signaling for cell survival.(1, 2) CD44 is encoded by the CD44 gene on chromosome 11. CD44 has been also been called Hermes antigen, lymphocyte homing receptor, ECM-III, and HUTCH-1.(2) CD44 function is controlled by its post-translational modifications and alternative splicing. One modification involves sialofucosylations which produces the selectin-binding form of CD44, HCELL (Hematopoietic Cell E-selectin/L-selectin Ligand).(3, 4) HCELL functions as a bone homing receptor, directing migration of human hematopoietic stem cells and mesenchymal stem cells to bone marrow. CD44 glycosylation also directly controls its binding capacity to fibrin and immobilized fibrinogen.(2) CD44 is a receptor for hyaluronic acid and can also interact with other ligands, such as osteopontin, collagens, MMPs, and Src.(2, 5) CD44 gene transcription is partly activated by catenin and Wnt.(1, 2)
Splice variants of CD44 on CRC cells display HCELL glycoforms. Variations in CD44 are reported as cell surface markers for some BC and PC stem cells. CD44 variant isoforms are also relevant to the progression of HNN.(1-4) It has been seen as an indicator of increased survival time in epithelial ovarian cancer patients. However, in many cancers (RCC and NHL are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. On the contrary, in some neoplasms CD44 upregulation is associated with a favorable outcome.(2)

Drugs/Indications
Trial Drugs/Interactions
Generic Code Old Code Brand Company Indication trials
OCZ103-OS Oncozyme P2: NSCLC, CRC trials
bivatuzumab BIWA Korea Otsuka; Boehringer Ingelheim P1: HNN, NSCLC, BC, squamous, adenocarcinoma, HCC (2013) trials
RO5429083 Roche P1: AML, solid trials
Failed Drugs/Interactions
Generic Code Old Code Brand Company Indication trials
tariquidar XR9576 QLT Last trial started in for oncology 2003; P3: NSCLC (terminated); P2: adrenal; P1: brain, Ewing's, BC, lung, ovarian trials
zosuquidar LY335979 Kanisa, Eli Lilly Last new trial 2005; P3: leukemia, myelodysplastic syndrome trials
PSC 833 noncorporate Last trial started in 2005; P2: BC; P3: leukemia; P1: RCC, lymphoma, solid trials


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References

1. Wang SJ, Wong G, de Heer AM, Xia W, Bourguignon LY. CD44 variant isoforms in head and neck squamous cell carcinoma progression. The Laryngoscope. 2009;119(8):1518-30.

2. Bluff JE BN, Reed MW, Staton CA. Tissue factor, angiogenesis and tumour progression. Breast Cancer Res. 2008;10(2):204. PMCID: 18373885.

3. Hanley WD, Burdick MM, Konstantopoulos K, Sackstein R. CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity. CANCER RESEARCH. 2005;65(13):5812-7.

4. Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E-and L-selectin in shear flow. Journal of Biological Chemistry. 2008;283(23):15647-55.

5. Bourguignon LY, Zhu H, Shao L, Chen Y-W. CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. Journal of Biological Chemistry. 2001;276(10):7327-36.

6. Khaldoyanidi S. Directing stem cell homing. Cell Stem Cell. 2008;2(3):198-200.