Differential expression of the CD44 molecule in human brain tumours

Kuppner, M. C.; Meir, Erwin G. Van; Gauthier, T; Mf, Hamou; Tribolet, N. De

doi:10.1002/ijc.2910500414

Cited by 115 publications

(48 citation statements)

References 18 publications

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“…The interaction between glioma and brain ECM components is, however, extremely complex and remains poorly understood. The recent finding that the expression of CD44 directly correlates with the highly invasive behavior of gliomas (14) establishes CD44 protein expression and functions as potential central nervous system tumor markers (38,39). Accordingly, CD44-mediated HA binding at the cell surface of gliomas is thought to involve multivalent binding events affected by the size of the HA ligand, the quantity and density of cell surface CD44, and the activation state of CD44 (40).…”

Section: Discussionmentioning

confidence: 98%

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Annabi

Thibeault

Moumdjian

et al. 2004

Journal of Biological Chemistry

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Hyaluronan (HA) is a component of the brain extracellular matrix environment that is synthesized and secreted by glioma cells. The primary cell surface receptor for HA is CD44, a membrane glycoprotein that is functionally regulated by a membrane type 1 matrix metalloproteinase (MT1-MMP). Both CD44 and MT1-MMP are partially located in Triton X-100-insoluble domains, but no functional link has yet been established between them. In the present study, we studied the regulation of HA cell surface binding in U-87 glioma cells. We show that an MMP-dependent mechanism regulates the intrinsic cell surface binding of HA as ilomastat, a broad MMP inhibitor, increased HA binding to glioma cells. HA binding was also rapidly and specifically up-regulated by 3-fold by type I collagen in U-87 cells, which also induced a significant morphological reorganization associated with the activation of a latent form of MMP-2 through a MT1-MMP-mediated mechanism. Interestingly, caveolae depletion with a cell surface cholesteroldepleting agent ␤-cyclodextrin triggered an additional increase (9-fold) in the binding of HA, in synergy with type I collagen. On the other hand, HA cell surface binding was diminished by the MEK inhibitor PD98059 and by the overexpression of a recombinant, wild type MT1-MMP, whereas its cytoplasmic-deleted form had no effect. Taken together, our results suggest that MT1-MMP regulates, through its cytoplasmic domain, the cell surface functions of CD44 in a collagen-rich pericellular environment. Additionally, we describe a new molecular mechanism regulating the invasive potential of glioma cells involving a MT1-MMP/CD44/caveolin interaction, which could represent a potential target for anti-cancer therapies.The principal molecules that have been identified in the normal brain extracellular matrix (ECM) 1 are hyaluronan (HA; also known as hyaluronic acid, hyaluronate) and chondroitin sulfate (1, 2). HA is an important glycosaminoglycan constituent believed to be implicated in angiogenesis, the formation of new blood vessels from preexisting vasculature. Although the serum level of HA is already used as an indicator of progressive malignant disease (3), its effects on in vivo angiogenesis and endothelial cell (EC) function are complex and have been reported to depend on HA concentration and molecular size (4, 5). Accordingly, whereas high molecular weight HA was shown to inhibit EC functions (6), low molecular weight HA stimulated EC proliferation, tubulogenesis (6, 7), and neovascularization (8). Moreover, small HA polymers efficiently regulated CD44 cell surface functional expression and promoted tumor cell migration (9). Astrocytic tumors of the central nervous system express CD44 among other cell adhesion receptors of the integrin or immunoglobulin superfamily. Although HA is the principal ligand of CD44, other CD44 ligands include the ECM components collagen, fibronectin, laminin, and chondroitin sulfate, whereas mucosal addressin, serglycin, osteopontin, and the class II invariant chain represent ECM-unrelat...

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Section: Discussionmentioning

confidence: 98%

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Annabi

Thibeault

Moumdjian

et al. 2004

Journal of Biological Chemistry

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“…In normal tissues the expression of such variants is mainly restricted to certain epithelia (Matsumura and Tarin, 1992; Foxet al, 1993; Heider et al, 1993a,h; Koopman et al, 1993;Li et al, 1993;Mackay et al, 1994;Sinn et al, 1994;Dall et al, 1994). In some tumors, e.g., medulloblastonia and endometrial cancer, only a few cases show low expression of CD44v (Kuppner et al, 1992; Fujita et al., 1994). In neuroblastomas, CD44 expression is correlated with a better survival prognosis (Favrot et al, 1993).…”

mentioning

confidence: 97%

Comparison of immunohistochemistry and RT‐PCR for detection of CD44v‐expression, a new prognostic factor in human breast cancer

Dall

Heider²,

Sinn

et al. 1995

Intl Journal of Cancer

142

100

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In different human tumors, splice variants of the surface glycoprotein CD44 (CD44v) are correlated with advanced stages of tumor growth and metastatic potential. In breast cancer and colon cancer, expression of epitopes encoded by exon v6 on primary tumors is an independent prognostic factor for poor patient survival. Two different screening methods for the detection of CD44 variants in tumors have been applied: immunohistochemistry (IHC) and semi-quantitative reverse transcription PCR (RT-PCR). In this study, we have compared the predictive capacity and the applicability of both approaches, using 31 human breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression of CD44v on normal ductal epithelial cells but strong expression on myoepithelial cells. The majority of tumors express CD44 epitopes encoded by several variant exons. RT-PCR detects splice variants in normal epithelium, probably derived from RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a wide range of splice variants, including new ones that are not detected in normal breast tissue, e.g. ones that contain all variant exons. The conclusion of this comparison is that IHC is the better method for breast-tumor sample screening but that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive from CD44v-negative tumors in cases where only a few tumor cells express variants or where epitopes are masked.

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“…The CD44 cell surface glycoprotein is thought to be involved in various aspects of cell-cell and cell-matrix adhesion [1,2], including lymphocyte homing [3,4], tumor cell adhesion, motility and invasion [5] as well as tumor growth [6], It has been found in a wide variety of normal human epithelial tissues, fibroblasts, smooth mus cle, most hematopoietic cell types, and in several tumors [7][8][9][10], A comparison of CD44 molecules derived from different tissues discloses extensive size heterogeneity. It is an acid-sulfated glycoprotein of cell membranes that contains multiple phosphoserine residues and several di sulfide bonds.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of CD44 Splice Variant Expression in Ovarian Cancer

et al. 1995

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In 44 ovarian cancers, CD44 variant (CD44v) expression was investigated immunohistochemically using a variant-specific polyclonal antibody. Patients with CD44v-positive carcinomas had a significantly shorter disease-free survival than patients with CD44v-negative tumors. Overall survival was also significantly reduced for stages III and IV of the International Federation of Gynecology and Obstetrics. Furthermore, a highly significant inverse correlation was observed between CD44v expression and preoperative platelet count. Urinary neopterin concentration, a marker of cell-mediated immunostimula-tion, did not differ between CD44v-positive and -negative ovarian cancer patients. Moreover, in seven ovarian carcinoma cell lines, modulation of CD44v expression was analyzed by living cell radioimmunoassay. Interferon-α, interferon-γ, tumor necrosis factor, transforming growth factor-β, all-trans retinoic acid and cisplatin did not affect CD44v expression.

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Differential expression of the CD44 molecule in human brain tumours

Cited by 115 publications

References 18 publications

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Comparison of immunohistochemistry and RT‐PCR for detection of CD44v‐expression, a new prognostic factor in human breast cancer

Prognostic Value of CD44 Splice Variant Expression in Ovarian Cancer

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