Expression of the Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) and the Matrix Metalloproteinase-2 in Bronchopulmonary and Breast Lesions

Caudroy, Stéphanie; Polette, Myriam; Tournier, Jean‐Marie; Burlet, Henriette; Toole, Bryan P.; Zucker, Stanley; Birembaut, Philippe

doi:10.1177/002215549904701209

Cited by 106 publications

(89 citation statements)

References 11 publications

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“…Thus far, only one immunohistochemical study on EMMPRIN expression in breast cancer tissue has been published, analyzing a small cohort of 20 patients (22) In contrast, we conducted a comprehensive analysis based on 1816 tumor samples, which led us to conclude that EMMPRIN expression is significantly correlated with risk factors such as poor histological grade, the mitotic index, tumor size, and most importantly, tumor-specific survival in human breast cancer, suggesting a crucial role of EMMPRIN in breast cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Expression of Extracellular Matrix Metalloproteases Inducer on Micrometastatic and Primary Mammary Carcinoma Cells

Reimers¹,

Zafrakas²,

Assmann³

et al. 2004

Clinical Cancer Research

131

109

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Purpose: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer.Experimental Design: An immunohistochemical study using high-density tissue microarrays (n ‫؍‬ 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2.Results: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P ‫؍‬ 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk ‫؍‬ 1.7, 95% confidence interval 1.4 -4.3, P ‫؍‬ 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on ϳ90% of micrometastatic cells in BM.Conclusions: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas.

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Section: Discussionmentioning

confidence: 99%

Expression of Extracellular Matrix Metalloproteases Inducer on Micrometastatic and Primary Mammary Carcinoma Cells

Reimers¹,

Zafrakas²,

Assmann³

et al. 2004

Clinical Cancer Research

131

109

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“…In addition to a paracrine stimulation by granulocytes expressing EMMPRIN, there may be an autocrine stimulation of fibroblasts to produce MMPs in the synovium. A recent study has demonstrated that EMMPRIN expression was present at the surface of both tumor epithelial cells and peritumor stromal cells from breast and lung tissues (18). Granulocytes from the peripheral blood of patients with RA express higher levels of EMMPRIN compared with healthy donors (19).…”

Section: Discussionmentioning

confidence: 99%

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

Tomita¹,

Nakase²,

Kaneko³

et al. 2002

Arthritis & Rheumatism

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Objective.To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) at sites of joint destruction in rheumatoid arthritis (RA) and to correlate it with the production of matrix metalloproteinases (MMPs).Methods. Reverse transcription-polymerase chain reaction was performed to study the existence of EMMPRIN in synovial tissue derived from RA and osteoarthritis (OA) patients. In situ hybridization with a human complementary DNA specific for EMMPRIN and immunohistochemistry were performed to characterize the EMMPRIN-expressing cells at sites of joint destruction, including bone. Northern blot analysis was performed to detect the level of expression of EMMPRIN messenger RNA (mRNA) in synovial tissue. The production of MMP-1 and MMP-3 by synovial tissue from RA patients was examined by enzyme-linked immunosorbent assay.Results. Expression of EMMPRIN mRNA was detected in synovium from 9 of 11 patients with RA and 1 of 5 patients with OA. The presence of mRNA encoding EMMPRIN was recognized in the invasive synovium at sites of joint destruction in RA but not OA.

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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). EMMPRIN expression has also been linked to tumor metastasis as it is one of the most constantly upregulated mRNAs in bone marrow metastatic cells in lung, prostate and breast cancer (Klein et al, 2002;Reimers et al, 2004).…”

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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Expression of the Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) and the Matrix Metalloproteinase-2 in Bronchopulmonary and Breast Lesions

Cited by 106 publications

References 11 publications

Expression of Extracellular Matrix Metalloproteases Inducer on Micrometastatic and Primary Mammary Carcinoma Cells

Expression of Extracellular Matrix Metalloproteases Inducer on Micrometastatic and Primary Mammary Carcinoma Cells

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

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

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