Functional Analysis of Four Tetraspans, CD9, CD53, CD81, and CD82, Suggests a Common Role in Costimulation, Cell Adhesion, and Migration: Only CD9 Upregulates HB-EGF Activity

Lagaudrière-Gesbert, Cécile; Naour, François Le; Lebel‐Binay, Sophie; Billard, Martine; Lemichez, Emmanuel; Boquet, Patrice; Boucheix, Claude; Conjeaud, Hélène; Rubinstein, Eric

doi:10.1006/cimm.1997.1223

Cited by 146 publications

(106 citation statements)

References 47 publications

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“…32 In addition, other tetraspans did not upregulate HB-EGF activities in hematopoietic cells. 33 In the present study, we demonstrated in vitro that SMCs promoted SMC growth in a juxtacrine manner, that CD9 and proHB-EGF were involved in the juxtacrine growth mechanism, and that coexpression of CD9 and proHB-EGF markedly stimulated SMC juxtacrine growth. Immunohistochemical analyses showed that some CD9-positive SMCs were localized adjacent to PCNA-positive SMCs.…”

Section: Discussionsupporting

confidence: 57%

Localization of CD9, an Enhancer Protein for Proheparin-Binding Epidermal Growth Factor–Like Growth Factor, in Human Atherosclerotic Plaques

Nishida

Miyagawa

Yamashita

et al. 2000

ATVB

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Abstract-Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a member of the EGF family, has a potent mitogenic activity for vascular smooth muscle cells (SMCs). We previously reported that HB-EGF is involved in atherogenesis of human aorta and coronary arteries. ProHB-EGF (the membrane-anchored form of HB-EGF) has also been demonstrated to possess a mitogenic activity, which is Ϸ30-fold increased when coexpressed with CD9 in mouse L cells. Thus, in the process of atherogenesis, CD9 may be involved in the proliferation of SMCs. We immunohistochemically investigated the localization of CD9 and proHB-EGF in the human aorta and coronary arteries. In normal aorta and coronary arteries, CD9 immunostaining was virtually negative, whereas proHB-EGF immunostaining was positive, especially in the arteries of babies. In contrast, in atherosclerotic lesions, some intimal SMCs were strongly positive for CD9 and proHB-EGF immunostaining. The juxtacrine growth activities of human aortic SMCs were inhibited in vitro by adding neutralization antibodies for CD9 or adding the specific inhibitor of HB-EGF. Besides, coexpressed CD9 and proHB-EGF cells markedly incorporated T he proliferation of vascular smooth muscle cells (SMCs) in the intima of arteries is one of the most important events in plaque formation 1 and in coronary restenosis after balloon angioplasty. 2 Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a member of the EGF family, has been identified as a potent mitogen for SMCs that is comparable to platelet-derived growth factor. 3 Localization and function of HB-EGF have been demonstrated in human hepatocellular carcinoma, 4 gastric mucosa, 5 wound fluid, 6 and balloon-injured rat carotid arteries. 7 Moreover, we have reported that HB-EGF is produced by macrophages and SMCs in the human aorta 8 and coronary arteries. 9 The HB-EGF precursor (proHB-EGF) is expressed on the cell membrane as a membrane-anchored form and can be cleaved to yield a mature biologically active form (soluble HB-EGF). 10 HB-EGF released by SMCs showed mitogenic function in an autocrine and a paracrine fashion. 11 Furthermore, proHB-EGF has also been demonstrated to have a mitogenic activity under the condition of cell-to-cell contact 12 by a so-called juxtacrine mechanism. 13 The juxtacrine growth factor activity of proHB-EGF in mouse L cells is dramatically upregulated Ϸ30-fold when coexpressed with CD9, 12 which was first identified as a cell surface antigen on lymphohematopoietic cells. 14,15 Thus, in the process of atherogenesis, CD9 may be involved in the proliferation of SMCs. In the present study, we investigated the immunohistochemical localization of CD9 and proHB-EGF in human coronary arteries and aorta and examined in vitro the effects of CD9 on the proliferation of human aortic SMCs.

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Section: Discussionsupporting

confidence: 57%

Localization of CD9, an Enhancer Protein for Proheparin-Binding Epidermal Growth Factor–Like Growth Factor, in Human Atherosclerotic Plaques

Nishida

Miyagawa

Yamashita

et al. 2000

ATVB

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“…This family also includes CD37, CD53, CD63, CD81, CD82, and CD151 (31). Although its exact function is unknown, previous studies implicated CD9 in cell adhesion, migration, or signal transduction (32)(33)(34). Biochemical studies have shown that CD9 is physically associated with various membrane proteins such as integrins (preferentially ␤ 1 integrin), MHC class II, CD19, CD5, or other tetraspanin members, depending on the cell types (32,(35)(36)(37)(38)(39).…”

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confidence: 99%

CD9 Is a Unique Marker for Marginal Zone B Cells, B1 Cells, and Plasma Cells in Mice

Won

Kearney

2002

The Journal of Immunology

146

115

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Marginal zone (MZ), follicular (FO), and B1 B cells form the long-lived naive B cell compartment. To identify surface markers that define MZ B cells in mice, we generated a panel of mAbs reactive with MZ but not FO B cells. One of these mAbs, MZ3, was found to recognize the tetraspanin CD9. CD9 expression not only distinguishes MZ B cells from FO B cells but also divided peritoneal cavity B1 cells into smaller subsets. After short-term in vitro stimulation with various mitogens, FO B cells failed to induce CD9 protein, while MZ B cells up-regulated the level of CD9 protein. However, after prolonged culture of FO B cells with LPS, surface CD9 was induced, together with syndecan 1, indicative of plasma cell differentiation. Following immunization with a T-independent-2 Ag, R36A, or a T-dependent Ag, SRBC, we found that CD9 is not expressed by germinal center B cells but is eventually expressed on plasma cells in response to both T-independent-2 and T-dependent Ags. Collectively, these results suggest that MZ B cells and B1 cell subsets are the immediate precursors of plasma cells in the primary response and that CD9 is acquired by T-dependent plasma cells.

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“…Tetraspanins have been detected both as free molecules, or interacting with different types of receptors, such as EGF-R, HB-EGF (Wang et al, 2002) or proteins with immunoglobulin domains, such as EWI-2 (Stipp et al, 2001); they also interact with MHC molecules and other membrane proteins, such as integrins, particularly those with the b1 subunit (Berditchevski, 2001;Boucheix and Rubinstein, 2001). Tetraspanin proteins can influence several biological processes, such as cell motility (Higashiyama et al, 1995;Miyake et al, 1995), and homotypic adhesion (Masellis-Smith et al, 1990;Lagaudriere-Gesbert et al, 1997;Lazo et al, 1997;Levy et al, 1998;Yanez-Mo et al, 1998;Shibagaki et al, 1999). There is a general consensus that tetraspanin molecules modulate interaction with the extracellular environment, and recently the specific interaction of CD9 with fibronectin has been characterized (Longhurst et al, 2002), but in general tetraspanin natural ligands are still unknown.…”

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confidence: 99%

Apoptosis protection and survival signal by the CD53 tetraspanin antigen

Yunta

Lazo

2003

Oncogene

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The CD53 antigen is a tetraspanin protein of the lymphoid-myeloid lineage, but its implication in biological effects is hardly known. Radioresistant tumor cells express very high levels of this antigen. We have studied the effect of CD53 antigen ligation on the survival response of tumor cells to serum deprivation, a wellknown stimulator of cell death that may mimic the tumor environment; for this aim IR938F and Jurkat cells, a Band T-cell lymphoma, were used. Ligation of CD53 triggers a survival response and reduces the number of cells that enter apoptosis. In CD53-stimulated cells there is a significant reduction in caspase activation, measured by caspase processing of poly ADP-ribose polymerase, as well as a reduction in the fragmentation of DNA. CD53-stimulated cells also have an increase in the level of bcl-X L and a reduction of bax protein, two components of the mitochondrial apoptotic pathway, changing their ratio by 24-fold in the direction of survival. This survival signal appears to be mediated by activation of the AKT, as detected by its phosphorylation in Ser473 upon CD53 ligation. The CD53 antigen interactions might contribute to cell survival in poorly vascularized regions of the tumor mass.

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Functional Analysis of Four Tetraspans, CD9, CD53, CD81, and CD82, Suggests a Common Role in Costimulation, Cell Adhesion, and Migration: Only CD9 Upregulates HB-EGF Activity

Cited by 146 publications

References 47 publications

Localization of CD9, an Enhancer Protein for Proheparin-Binding Epidermal Growth Factor–Like Growth Factor, in Human Atherosclerotic Plaques

Localization of CD9, an Enhancer Protein for Proheparin-Binding Epidermal Growth Factor–Like Growth Factor, in Human Atherosclerotic Plaques

CD9 Is a Unique Marker for Marginal Zone B Cells, B1 Cells, and Plasma Cells in Mice

Apoptosis protection and survival signal by the CD53 tetraspanin antigen

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