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CD44 Expression
Published by Anonymous on 2007/9/30 (1890 reads)
1: Arch Immunol Ther Exp (Warsz). 2004 Jan-Feb;52(1):13-26.


Recent advances in the regulation of CD44 expression and its role in inflammation and autoimmune diseases.

Gee K, Kryworuchko M, Kumar A.

Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.

Interaction of CD44, an adhesion molecule, with its extracellular matrix ligand, hyaluronan (HA), has been suggested to play a critical role in a number of biological manifestations, including cell migration, tumorigenesis, metastasis, and regulation of immune responses. CD44 comprises a large family of transmembrane glycoproteins that exhibit extensive molecular heterogeneity. This heterogeneity in size is generated by alternative RNA splicing of variable exons as well as by post-translational modifications. Most cell types express CD44 but do not bind HA. The biological functions of CD44, including the regulation of lymphocyte recruitment to the sites of inflammation, have been attributed to the generation of a functionally active, HA-adhesive phenotype. The molecular mechanisms underlying the regulation of CD44 expression and the generation of a functionally active HA-binding phenotype are not well understood. Recently, CD44-HA interactions have been reported to play a critical role in a number of autoimmune diseases in humans and experimental animal models. Initial studies have taken advantage of anti-CD44 antibodies which specifically block CD44-HA interactions. Administration of these antibodies in several experimental murine models of autoimmune diseases resulted in alleviation of inflammatory reactions. In addition, the generation of CD44-deficient animals has facilitated our understanding of the involvement of CD44 in inflammation and autoimmune diseases. This review will focus on the recent advances in the molecular mechanisms regulating CD44 expression, ligand binding, as well as the contribution of CD44 to the development of inflammation and autoimmune disorders.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15053229 [PubMed - indexed for MEDLINE]

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2: Adv Cancer Res. 2000;77:169-87.


CD44 glycoproteins in colorectal cancer: expression, function, and prognostic value.

Wielenga VJ, van der Neut R, Offerhaus GJ, Pals ST.

Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 10549358 [PubMed - indexed for MEDLINE]

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3: Zhonghua Fu Chan Ke Za Zhi. 1997 Dec;32(12):756-62.


[CD44 gene expression and gynecologic neoplasms]

[Article in Chinese]

Qu F, Jiao S.

Publication Types:
Review

PMID: 9772442 [PubMed - indexed for MEDLINE]

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4: Nippon Geka Gakkai Zasshi. 1998 Jul;99(7):409-14.


[Expression of variant CD44 in colorectal cancer and its relationship to liver metastasis]

[Article in Japanese]

Yamaguchi A.

First Department of Surgery, Fukui Medical University School of Medicine, Japan.

A number of different isoforms of CD44 generated by alternative splicing have been isolated and sequenced. There have been several reports that CD44v plays a role in the steps of the metastatic process. We examined the role of the variant CD44v8-10 in metastases of human colon cancer cell line HT29m using a monoclonal antibody reactive with the v9 product (mAb 44-1V). Pretreatment with mAb 44-1V prevented the formation of liver metastases. In addition, we found that the attachment of HT29m cells to the basement membrane matrix was inhibited by mAb 44-1V. Several reports have shown correlations between metastatic potential and expression of CD44v in human colorectal cancer. We demonstrated that CD44v8-10 and CD44v6 RNA expression was higher in carcinomas associated with liver metastases than in those without by Northern blotting. We analyzed the expression of the CD44v8-10 product in colorectal cancer immunohistochemically using mAb 44-1V, and evaluated its prognostic significance. There were significant correlations between CD 44v8-10 immunoreactivity and both lymph node and liver metastases. Patients with CD44v8-10-positive tumors had a greater relative risk of death compared with those whose tumors were CD44v8-10 negative. These results suggest that CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance.

Publication Types:
English Abstract
Review

PMID: 9742519 [PubMed - indexed for MEDLINE]

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5: Front Biosci. 1998 Jul 1;3:d657-64.


CD44 expression and growth factors.

Hamada J, Sawamura Y, Van Meir EG.

Division of Cell Biology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan. jhamada@med.hokudai.ac.jp

Soluble factors such as growth factors and cytokines present in the tumor microenvironment regulate a variety of genes associated with malignant properties of tumor cells such as growth, migration, invasion, and metastatic capacities. CD44 is a multi-functional adhesion molecule involved in cell to cell and cell to extracellular matrix interaction, the trapping of growth factors and cytokines, and the regulation of cell traffic. Growth factors and cytokines modify the expression, selective isoform splicing and functions of CD44, resulting in changes in the biological properties of the cells. These include adhesion of circulating tumor cells to endothelium and body cavities, and survival in response to growth factors presented by the CD44 molecule. The modification of CD44 on both tumor and host cells by growth factors may play an important role in tumor progression.

Publication Types:
Review

PMID: 9634542 [PubMed - indexed for MEDLINE]

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6: Front Biosci. 1998 Jul 1;3:e89-109.


Clinical implications of anomalous CD44 gene expression in neoplasia.

Goodison S, Tarin D.

UCSD Cancer Center 9500 Gilman Drive, La Jolla, California 92093, USA.

An intensive search continues for reliable markers that would be clinically useful in the diagnosis of small tumors and in the evaluation of their predicted clinical outcome. One potential marker, extensively studied in human samples is the cell surface adhesion molecule CD44. The single CD44 gene codes for a large family of cell surface proteins by alternative splicing and severe abnormalities have been observed in the patterns of its expression in many types of human tumors using both protein and RNA-based analyses. These abnormalities are manifested by markedly increased levels of unusual transcripts and proteins in tumor cells compared to the corresponding normal tissues. Aberrant processing of immature CD44 transcripts has also been observed in tumor cells and this can lead to the inappropriate retention of introns and to the use of cryptic splice sites in the mRNA. Inappropriate expression patterns of the alternatively spliced exons have also been linked both to tumor progression and to metastatic potential. The clinical relevance of all these observations is demonstrated by the frequent detection of these abnormalities in samples from malignant tumors of many different organs and by their presence in pre-invasive and high risk pre-cancerous lesions. This article reviews the current information regarding the expression of the CD44 gene in tumor cells and its potential use as a marker in clinical evaluation. The overall conclusion is that with the use of the latest assay techniques and perhaps in combination with other molecular markers, analysis of CD44 expression can provide new and powerful assays for the detection of neoplastic disease.

Publication Types:
Review

PMID: 9634541 [PubMed - indexed for MEDLINE]

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7: Nippon Rinsho. 1997 Feb;55(2):381-5.


[Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant]

[Article in Japanese]

Chong JM, Fukayama M.

First Department of Pathology, Jichi Medical School.

Epstein-Barr virus (EBV), a ubiquitous human herpes virus, was recently identified in 2-16% of gastric carcinomas. EBV-encoded small RNA was found in nearly all of the carcinoma cells even at the intramucosal stage. EBV in EBV associated gastric carcinoma (EBVaGC) is monoclonal based on Southern blot hybridization using probes adjacent to the unique terminal repeat of EBV-DNA. Furthermore, the genetic pathway of this carcinogenesis is different of EBVaGC: deletion of 5q and/or 17p and microsatellite instability are extremely rare in EBVaGC, in contrast to their high frequency in EBV-negative carcinomas. We also examined the relationship between the expression of CD44 variants and EBVaGC, and found the expression of CD44 variants was significantly correlated with EBV-etiology.

Publication Types:
English Abstract
Review

PMID: 9046827 [PubMed - indexed for MEDLINE]

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8: J Neurooncol. 1995 Dec;26(3):191-8.


Expression of the CD44 adhesion molecule in tumours of the central and peripheral nervous system.

Baltuch GH, de Tribolet N, Van Meir EG.

Department of Neurosurgery, University Hospital (CHUV), Lausanne, Switzerland.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 8750185 [PubMed - indexed for MEDLINE]

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9: J Mol Med. 1995 Sep;73(9):425-38.


CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation.

Zöller M.

Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany.

Continuous progress has been achieved during recent decades in the therapy of metastasizing malignancies by improving chemotherapeutic strategies and new approaches in radiation therapy. Genetic manipulation of tumor cells and of the tumor fighting immune system is hoped to add significant contributions to curative interventions in disseminated tumors. That we are still far from eradicating death by malignant growth is due ultimately to our limited understanding of the cascade of events resulting in metastasis formation, which until recently was believed to rely on multiple rounds of mutation and selection processes. This implies an individually specific history of each metastatic tumor, which would rule out uniform diagnostic and therapeutic concepts. When it was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44 variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis formation of a locally growing tumor, hope was created that a "metastogene" may have been identified. Although the idea of CD44v expression as a unifying concept for tumor progression was not sustained, the discovery of CD44v-initiated metastatic spread allowed a conceptually new hypothesis on tumor progression as a consequence of the reactivation of genetic programs of ontogeny, stem cell differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play an important role in these processes, unraveling the functions of this family of molecules can indeed provide a cornerstone in the understanding of tumor progression. This article summarizes briefly the present knowledge on known functions of CD44 isoforms with particular focus on parallels between physiological programs and tumor progression.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 8528746 [PubMed - indexed for MEDLINE]

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10: Nippon Rinsho. 1995 Jul;53(7):1710-5.


[Expression of CD44 variant form in human renal cell carcinoma]

[Article in Japanese]

Kanayama H, Kan M, Aki M, Kagawa S.

Department of Urology, School of Medicine, University of Tokushima.

To examine whether renal cell carcinoma display altered CD44 expression we performed reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CD44 in the tissues resected from 19 patients with renal cell carcinoma and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT-PCR Southern blot method reported by Matsumura et al. In 12 of 17 (70.6%) cases, about a 700 base pairs band was emphasized in cancerous tissues compared with normal kidney. Moreover, we found that this isoform is the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 variants sharing exon v10. Our findings suggest that this variant form plays some roles in renal cell carcinoma.

Publication Types:
English Abstract
Review

PMID: 7630012 [PubMed - indexed for MEDLINE]

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11: Nippon Rinsho. 1995 Jul;53(7):1699-703.


[Expression of CD44 metastatic variant mRNA in colorectal carcinomas and its role in tumor metastasis and invasion]

[Article in Japanese]

Sugaya Y, Harigaya K.

Department of 1st Pathology, School of Medicine, Chiba University, Japan.

The expression of CD44 molecules was investigated in colorectal carcinomas by RT-PCR and Southern Blot Analysis. There were significant differences between neoplastic and non-neoplastic colonic mucosa in the expression of CD44 metastatic variant mRNA. The CD44 metastatic variant mRNA was found to be increased in the neoplastic mucosa. However, we could not find metastasis-specific transcript in primary colorectal carcinomas. Our study suggests that the neoplastic transformation of colonic mucosa increases the expression of CD44 molecules, including the variant forms, which modulate the behavior of the tumor cells. The measurement of serum CD44 is useful in the estimation of tumor mass and its regression by treatment. Further investigation is needed to clearly understand the role of CD44 molecules in tumor metastasis and invasion.

Publication Types:
English Abstract
Review

PMID: 7630010 [PubMed - indexed for MEDLINE]

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12: Invasion Metastasis. 1994-1995;14(1-6):156-63.


Expression of integrin and CD44 adhesion molecules on neuroblastoma: the relation to tumor aggressiveness and embryonic neural-crest differentiation.

Combaret V, Coll JL, Favrot MC.

Laboratory of Cellular Biology, Centre Léon-Bérard, Lyon, France.

The immunohistological expression of integrins and CD44 cell adhesion molecule was analyzed on neuroblastoma (NB) specimens to study the potential role of these molecules in normal differentiation and in the transformation of neural crest derivatives. None of the specimens expressed the alpha 5 beta 1 integrin heterodimer; the expression of alpha 3 beta 1 heterodimer was maintained during all stages of differentiation; alpha 1 beta 1 heterodimer was expressed on undifferentiated neuroblasts and on Schwann cells, but was lost on ganglion cells. In contrast alpha 2 beta 1, alpha 6 beta 1, alpha 6 beta 4 and alpha V beta 1 expression was usually restricted to cells differentiated in the Schwann cell lineage. Alpha V beta 3 was expressed on tumors developed in the mediastinum. CD44 was strongly detected on differentiated ganglioneuroblastomas, stage 1 and 2 ganglioneuromas, as well as low-grade stage 4S NB and normal neuroblasts migrating in the fetal adrenal gland. CD44 expression was observed on Schwann cells and ganglion cells; in contrast, it was expressed on only 50% stage 3 and 4 undifferentiated NB. None of these specimens expressed exons V5, V7 or V6. In a few specimens, an intracellular expression of exons V8-V10 was observed in ganglion cells. The expression of CD44 on NB may reflect its pattern of expression on sympatho-adrenal precursors and arrest differentiation at these stages. Conversely, CD44 expression may be silenced during malignant transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:
Review

PMID: 7544774 [PubMed - indexed for MEDLINE]

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13: Res Immunol. 1993 Nov-Dec;144(9):750-4; discussion 754-62.


CD44 splice variants; expression on lymphocytes and in neoplasia.

Koopman G, Griffioen AW, Ponta H, Herrlich P, van den Berg F, Manten-Horst E, Pals ST.

Department of Pathology, University of Amsterdam.

Publication Types:
Review

PMID: 7512745 [PubMed - indexed for MEDLINE]

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14: Behring Inst Mitt. 1993 Aug;(92):273-7.


CD44 splice variants: expression during lymphocyte activation and tumor progression.

Pals ST, Koopman G, Heider KH, Griffioen A, Adolf GR, Van den Berg F, Ponta H, Herrlich P, Horst E.

Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.

A recently described splice variant of CD44 has been shown to confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins in human lymphoid cells and tissues, in non-Hodgkin's lymphomas, and in colorectal neoplasia. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, while T lymphocytes, upon activation by mitogen or antigen, transiently upregulate expression of specific CD44 variant glycoproteins. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability. Interestingly, overexpression of v6 was also found in several aggressive, but not in low-grade, non-Hodgkin's lymphomas (NHL). In human colorectal neoplasia we also observed strong overexpression of CD44 splice variants in all invasive carcinomas and carcinoma metastasis. Interestingly, focal expression was already observed in adenomatous polyps, expression being related to areas of dysplasia. The findings establish CD44 variants as tumor progression markers in colorectal cancer.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7504454 [PubMed - indexed for MEDLINE]
 

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