A Role for CD147 in Thymic Development

Renno, Toufic; Wilson, Anne; Dunkel, Caroline; Coste, Isabelle; Maisnier-Patin, Karine; Coignac, Amélie Benoit de; Aubry, Jean‐Pierre; Lees, Rosemary K.; Bonnefoy, Jean‐Yves; MacDonald, H. Robson; Gauchat, Jean‐François

doi:10.4049/jimmunol.168.10.4946

Cited by 59 publications

(47 citation statements)

References 30 publications

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“…Impaired spermatogenesis (arrest at the metaphase of the first meiosis) is observed in EMMPRIN null male mice (Igakura et al, 1998), whereas the female sterility is thought to be caused by the failure of fertilization and implantation (Igakura et al, 1998). EMMPRIN null mice also have several neurological and cognitive defects, reduced blood-brain barrier integrity (Igakura et al, 1996), and cycling defects in lymphocytes (Renno et al, 2002). Together, this has made EMMPRIN null mice a poor candidate to investigate EAE in our opinion.…”

Section: Discussionmentioning

confidence: 98%

EMMPRIN: A Novel Regulator of Leukocyte Transmigration into the CNS in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Agrawal¹,

Silva²,

Tourtellotte³

et al. 2011

J. Neurosci.

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Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a member of the Ig superfamily, with various physiological roles including the induction of matrix metalloproteinases (MMPs), leukocyte activation, and tumor progression. In this study, we illustrate a novel involvement of EMMPRIN in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We found EMMPRIN levels to be upregulated on peripheral leukocytes before onset of EAE clinical signs and on infiltrating leukocytes and resident cells within the CNS in symptomatic mice. In EAE brain sections, EMMPRIN expression was localized with MMP-9 protein and activity. The increased EMMPRIN level was also characteristic of brain samples from MS subjects, particularly in plaque-containing areas. To evaluate the implications of elevated EMMPRIN levels, we treated EAE mice with an EMMPRIN function-blocking antibody and found reduced EAE clinical severity accompanied by decreased CNS parenchymal infiltration of leukocytes. Amelioration of EAE clinical signs by the anti-EMMPRIN antibody was critically dependent on its administration around the period of onset of clinical signs, which is typically associated with significant influx of leukocytes into the CNS. Moreover, the reduction in disease severity in anti-EMMPRINtreated mice was associated with diminished MMP proteolytic activity at the glia limitans, the final barrier before parenchymal infiltration of leukocytes. Together, our results are the first to emphasize a role for EMMPRIN in MS and EAE, whereby EMMPRIN regulates leukocyte trafficking through increasing MMP activity. These results identify EMMPRIN as a novel therapeutic target in MS.

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Section: Discussionmentioning

confidence: 98%

EMMPRIN: A Novel Regulator of Leukocyte Transmigration into the CNS in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Agrawal¹,

Silva²,

Tourtellotte³

et al. 2011

J. Neurosci.

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“…While the pre-TCR signaling complex, comprised of TCRβ chain, pTα and a functional CD3 complex, was found to regulate selection / survival, evidence suggests that CD147 ligation can serve as the second signal necessary for expansion (Renno et al 2002). Within the thymus, CD147 expression is highest on late stage, immature thymocytes, which correlates with transition to the next maturational level.…”

Section: Role In Lymphocyte Migration and Activationmentioning

confidence: 99%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

243

206

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The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

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“…It is believed to have a significant role in the development, differentiation and remodeling of many normal tissues including the lung, thymus, retina, skin, cornea and nervous system (Renno et al, 2002;Betsuyaku et al, 2003;Gabison et al, 2005;Nabeshima et al, 2006). However, it is in the field of cancer that EMMPRIN has garnered most interest because of its consistently high levels of expression on the surface of various tumors, including lung tumors, and because of its correlation with poor prognosis (Caudroy et al, 1999;Davidson et al, 2003;Yan et al, 2005;Riethdorf et al, 2006;Als et al, 2007;Sienel et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

EMMPRIN regulates the canonical Wnt/β-catenin signaling pathway, a potential role in accelerating lung tumorigenesis

et al. 2010

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Advances in the field of tumor biology have identified that tumor cells co-opt developmental signaling pathways of embryonic stem cells and thus gain the ability to proliferate, differentiate and alter cell-cell interactions. One such pathway is the Wnt/b-catenin signaling pathway. High levels of EMMPRIN expression have been shown to correlate with poor prognosis and metastasis in a broad range of tumors. Although a variety of functions are attributed to EMMPRIN in tumorigenesis, the specific mechanism(s) through which it can exert its effects have not been elucidated, until now. In this study, we identify EMMPRIN as a novel regulator of the canonical Wnt/ b-catenin signaling pathway in lung cancer. Increasing EMMPRIN expression levels in lung cancer epithelial cells upregulated the b-catenin signaling pathway and silencing EMMPRIN inhibited b-catenin signaling, cell migration, proliferation, anchorage-independent growth and tumor growth in a mouse tumor xenograft model. These results provide a compelling rationale for targeting EMMPRIN for anticancer therapies. Understanding the molecular mechanisms driving EMMPRIN-induced lung tumorigenesis will provide enormous benefits in developing new therapeutic treatments for this and other forms of cancer.

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A Role for CD147 in Thymic Development

Cited by 59 publications

References 30 publications

EMMPRIN: A Novel Regulator of Leukocyte Transmigration into the CNS in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

EMMPRIN: A Novel Regulator of Leukocyte Transmigration into the CNS in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

CD147 immunoglobulin superfamily receptor function and role in pathology

EMMPRIN regulates the canonical Wnt/β-catenin signaling pathway, a potential role in accelerating lung tumorigenesis

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