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Emmprin in epithelioid sarcoma: Expression in tumor cell membrane and stimulation of MMP‐2 production in tumor‐associated fibroblasts
Author(s) -
Koga Kaori,
Nabeshima Kazuki,
Aoki Mikiko,
Kawakami Takehito,
Hamasaki Makoto,
Toole Bryan P.,
Nakayama Juichiro,
Iwasaki Hiroshi
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22412
Subject(s) - matrix metalloproteinase , stromal cell , gelatinase , cancer research , immunohistochemistry , chemistry , pathology , gelatinase a , zymography , metastasis , downregulation and upregulation , metalloproteinase , biology , medicine , cancer , biochemistry , gene
Emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMPs). Emmprin and the induced MMPs play a crucial role in tumor progression, invasion and metastasis of human carcinomas (epithelial malignancies). However, only a few reports have addressed its role in soft tissue sarcomas. This study investigated the expression and role of emmprin in epithelioid sarcoma (ES). Immunoblot studies of 2 ES cell lines showed that they express emmprin, and co‐culture of these ES cells with dermal fibroblasts resulted in upregulation of gelatinase A (MMP‐2) in fibroblasts, as shown by zymography, immunoblotting and enzyme immunoassay. This stimulation was inhibited by an activity‐blocking peptide against emmprin and by antiemmprin antibody. In addition, in vivo , immunohistochemical analysis of 5 ES patient cases demonstrated diffuse emmprin expression in ES cells and MMP‐2 expression in both ES cells and peritumoral fibroblasts. The histopathological findings that peritumoral fibroblasts that were not in direct contact with emmprin‐expressing ES cells exhibit upregulated MMP‐2 prompted us to look for a soluble form of emmprin. Soluble full‐length emmprin released from ES cells was detected in conditioned medium and shown to stimulate MMP‐2 production by fibroblasts. In conclusion, emmprin is expressed in ES in both membrane and soluble forms and stimulates MMP‐2 production via interactions with fibroblasts, which could play a role in ES cell stromal invasion and vascular involvement. © 2006 Wiley‐Liss, Inc.