CD44 as a potential diagnostic tumor marker

CD44 is a cellular protein that has been intensively studied in relation to carcinogenesis over the last decade. It is altered during inflammatory responses and cellular malfunctioning during tumor progression. Tumors of epithelial origin express CD44 in multiple isoforms called variants; some isoforms are related to specific cancer cells. An increase of CD44 specific isoforms is detected in certain leukemic proliferations. Most published data indicates a partial involvement of CD44 in cancer cells, either in invasiveness or self-renewability. However, there is still uncertainty regarding the exact mechanism by which CD44 participates in growth of cancer or the inflammatory response. This review focuses on CD44 prevalence in cancer cell. It considers tumorigenic behavior of cells that highly express CD44 as an early marker for neoplastic stem cell proliferation. We will discuss multiple examples of tumor in this paper, with an emphasis of 2 solid tumors; namely, breast and colon cancer.

[1]  P. Lansdorp,et al.  Differentiation-associated changes in CD44 isoform expression during normal hematopoiesis and their alteration in chronic myeloid leukemia. , 1995, Blood.

[2]  L. Rassenti,et al.  Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44 , 2013, Proceedings of the National Academy of Sciences.

[3]  Viraj J. Jasinghe,et al.  Inhibition of CD44 expression in hepatocellular carcinoma cells enhances apoptosis, chemosensitivity, and reduces tumorigenesis and invasion , 2008, Cancer Chemotherapy and Pharmacology.

[4]  M. Hung,et al.  Interaction between the Adhesion Receptor, CD44, and the Oncogene Product, p185 HER2 , Promotes Human Ovarian Tumor Cell Activation* , 1997, The Journal of Biological Chemistry.

[5]  M. Watabe,et al.  Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells. , 2012, Cancer research.

[6]  N. Dalay,et al.  CD44 variant exons in leukemia and lymphoma , 2009, Pathology Oncology Research.

[7]  P. Frenette,et al.  Alternative CD44 splicing in intestinal stem cells and tumorigenesis , 2014, Oncogene.

[8]  M. A. Abdelaal,et al.  Elevated cerebrospinal fluid beta-2 microglobulin as a tumor marker in a patient with myeloma of the central nervous system. , 2007, Saudi medical journal.

[9]  J. Dick,et al.  Targeting of CD44 eradicates human acute myeloid leukemic stem cells , 2006, Nature Medicine.

[10]  Nicholas H Brown,et al.  Integrins and the actin cytoskeleton. , 2007, Current opinion in cell biology.

[11]  A. Afify,et al.  Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion. , 2009, Experimental and molecular pathology.

[12]  G. Sconocchia,et al.  CD44 ligation on peripheral blood polymorphonuclear cells induces interleukin-6 production. , 2001, Blood.

[13]  C. Kuperwasser,et al.  Human breast cancer stem cell markers CD44 and CD24: enriching for cells with functional properties in mice or in man? , 2007, Breast Cancer Research.

[14]  Tao Wang,et al.  HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells. , 2011, Gastroenterology.

[15]  A. Freeman,et al.  Differential Expression of CD44 During Human Prostate Epithelial Cell Differentiation , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  A. Phillips,et al.  Hyaluronan Facilitates Transforming Growth Factor-β1-dependent Proliferation via CD44 and Epidermal Growth Factor Receptor Interaction , 2011, The Journal of Biological Chemistry.

[17]  Premkumar Vummidi Giridhar,et al.  CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches , 2013, Experimental biology and medicine.

[18]  M. Leibovitch,et al.  CD44: a new means to inhibit acute myeloid leukemia cell proliferation via p27Kip1. , 2004, Blood.

[19]  Susan G Hilsenbeck,et al.  Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. , 2008, Journal of the National Cancer Institute.

[20]  K. Gee,et al.  Recent advances in the regulation of CD44 expression and its role in inflammation and autoimmune diseases. , 2004, Archivum immunologiae et therapiae experimentalis.

[21]  M. Zöller.  CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? , 2011, Nature Reviews Cancer.

[22]  R. V. van Etten.  New insights into the normal and leukemic stem cell niche: A timely review , 2013, Cytometry. Part B, Clinical cytometry.

[23]  M. Ringnér,et al.  CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers , 2011, BMC Cancer.

[24]  J. Sleeman,et al.  Targeting dendritic cells with CD44 monoclonal antibodies selectively inhibits the proliferation of naive CD4+ T‐helper cells by induction of FAS‐independent T‐cell apoptosis , 2003, Immunology.

[25]  M. Pollak,et al.  The Type 1 Insulin-Like Growth Factor Receptor Pathway , 2008, Clinical Cancer Research.

[26]  M. Nagarkatti,et al.  CD44 mobilization in allogeneic dendritic cell–T cell immunological synapse plays a key role in T cell activation , 2008, Journal of leukocyte biology.

[27]  K. Bennett,et al.  CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor , 1995, The Journal of cell biology.

[28]  D. Vrdoljak,et al.  The relation between tumor marker Ca 15-3 and metastases in interpectoral lymph nodes in breast cancer patients. , 2006, Saudi medical journal.

[29]  R. A. Etten.  New insights into the normal and leukemic stem cell niche: a timely review. , 2013 .

[30]  M. Ohmura,et al.  CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. , 2011, Cancer cell.

[31]  S. Yuruker,et al.  Immunohistochemical analysis of CD31, CD36, and CD44 antigens in human omentum. , 2004, Saudi medical journal.

[32]  A. Ullrich,et al.  Receptor tyrosine kinase signalling as a target for cancer intervention strategies. , 2001, Endocrine-related cancer.