Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer

Jagt, Michel F. van der; Sweep, Fred C.G.J.; Waas, Erwin T.; Hendriks, T.; Ruers, Theo J.M.; Merry, Audrey H H; Wobbes, Theo; Span, Paul N.

doi:10.1016/j.canlet.2005.06.009

Cited by 56 publications

(57 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, we speculate that EMMPRIN might be involved in stromal remodelling and epithelial repair after injury. Compared with gastric normal, hyperplastic or metaplastic mucosa, gastric carcinoma highly expressed EMMPRIN protein in line with other malignancies (Davidson et al, 2003;Ishibashi et al, 2004;Marieb et al, 2004;Li et al, 2005;Tang et al, 2005;Zhou et al, 2005;Sier et al, 2006;van der Jagt et al, 2006). Additionally, strong expression was also observed in gastric carcinoma cell lines in our study.…”

Section: Discussionsupporting

confidence: 78%

“…Elevated EMMPRIN expression has also been shown to correlate with the progression of various malignancies (Davidson et al, 2003;Ishibashi et al, 2004;Marieb et al, 2004;Gabison et al, 2005a, b;Li et al, 2005;Tang et al, 2005;Zhou et al, 2005;Sier et al, 2006;van der Jagt et al, 2006). Our results indicated that EMMPRIN overexpression was positively linked to tumour size of gastric carcinoma.…”

Section: Discussionsupporting

confidence: 63%

“…A large body of evidence indicates that increased soluble EMMPRIN released from cancer cells can stimulate the MMP synthesis and activation of surrounding stromal cells so as to promote the progression of tumours (Yoshida et al, 2000;Sun and Hemler, 2001;Davidson et al, 2003;Muramatsu and Miyauchi, 2003;Ishibashi et al, 2004;Marieb et al, 2004;Gabison et al, 2005a, b;Li et al, 2005;Tang et al, 2005;Zhou et al, 2005;Sier et al, 2006;van der Jagt et al, 2006). Recently, Tang et al (2004) indicated that elevation of MMPs mediated by EMMPRIN could result in more proteolytic cleavage of membrane-associated EMMPRIN, forming a positive feedback tumour-stoma interaction.…”

Section: Discussionmentioning

confidence: 99%

“…Cotransfection of EMMPRIN expression vectors with different tags and crosslinking experiments have suggested that the molecules could associate with each other on the plasma membrane, forming homo-oligomers in a cisdependent manner via the N-terminally located Ig-like domain (Yoshida et al, 2000;Sun and Hemler, 2001). Although EMMPRIN has a broader tissue distribution and is expressed on activated T cells, on differentiated macrophage, on retinal pigment epithelium, in the endometrium and in normal human keratinocytes, its expression is often elevated on breast cancers, hepatomas, oesophageal and cervical squamous cell carcinomas, colorectal and ovarian carcinomas, which increases tumour invasion by inducing MMP synthesis of surrounding stromal cells, including membrane type 1 and type 2 MMP, and the endogenous activators of MMP-2 (Davidson et al, 2003;Ishibashi et al, 2004;Marieb et al, 2004;Gabison et al, 2005a, b;Li et al, 2005;Tang et al, 2005;Zhou et al, 2005;Sier et al, 2006;van der Jagt et al, 2006). Recently, various in vivo evidences indicated that EMMPRIN might stimulate tumour angiogenesis by elevating VEGF and MMP expression in the neighbouring fibroblasts and epithelial cells in a paracrine manner (Tang et al, 2005).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

et al. 2006

View full text Add to dashboard Cite

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n ¼ 234) and non-cancerous mucosa adjacent to carcinoma (n ¼ 85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (Po0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (Po0.05), but not with lymph node metastasis, UICC staging or differentiation (P40.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (Po0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (Po0.05), but not be independent factor for prognosis (P40.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Clinicopathological studies with cancer patients have demonstrated that high RECK expression is significantly correlated with good prognosis (Furumoto et al, 2001;Masui et al, 2003;Span et al, 2003;Takenaka et al, 2004Takenaka et al, , 2005van der Jagt et al, 2005). However, the positive control mechanism of the RECK gene expression has not been studied yet, though the rasmediated downregulation was studied (Sasahara et al, 2002).…”

mentioning

confidence: 99%

TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118

Diaz

Wei

et al. 2006

Oncogene

View full text Add to dashboard Cite

We previously demonstrated that TIMP-2 increases the association of Crk with C3G and via subsequent activation of Rap1 enhances the expression of RECK, a membrane-anchored MMP inhibitor. In the present study, we investigate the mechanism of how the TIMP-2 signal is transduced from the a3b1 integrin receptor to the Crk-C3G-Rap1 molecular complex. TIMP-2 treatment of human microvascular endothelial cells (hMVECs) increased the phosphorylation levels of Src at Tyr-527, the negative regulatory site, through enhanced association of Src with Csk. This results in the reduction of Src kinase activity and dephosphorylation of paxillin at Tyr-31/118, the target sites for Src kinase phosphorylation and also the binding sites for the downstream effector Crk. Such TIMP-2 effects accompany the disassembly of paxillinCrk-DOCK180 molecular complex and, in turn, Rac1 inactivation. On the contrary, levels of paxillin-Crk-C3G complex formation are not reduced, rather slightly increased, which is consistent with our previous finding. Therefore, TIMP-2-mediated inhibition of Src kinase activity leads to the signaling switch from Rac1 to Rap1, thereby leading to enhanced RECK expression.

show abstract

Prognostic impact of extracellular matrix metalloprotease inducer

Buergy

Fuchs

Kambakamba

et al. 2009

Cancer

View full text Add to dashboard Cite

BACKGROUND: Extracellular matrix metalloprotease inducer (EMMPRIN) induces matrix metalloproteinase (MMP) expression, tumor‐stroma cell interaction, and invasion/angiogenesis. The objectives of the current study were to find the first evidence of a prognostic impact of total and relative EMMPRIN expression in colorectal cancer cells and to analyze EMMPRIN in bone marrow‐disseminated tumor cells and normal cells from 2 different gastrointestinal cancer entities. METHODS: Tumors and normal tissues from 40 patients with colorectal cancer who were followed prospectively (median follow‐up, 31 months) were analyzed for EMMPRIN by immunohistochemistry. Bone marrow from 51 patients (13 patients with gastric cancer and 38 patients with colorectal cancer) with evidence of disseminated tumor cells was screened for EMMPRIN in tumor cells and normal cells (cytokeratin 18/EMMPRIN double immunocytochemistry). RESULTS: A significant correlation between poor disease‐specific survival (P = .037; Kaplan‐Meier method; Mantel‐Cox log‐rank tests) and an increased ratio of EMMPRIN in tumor cells versus corresponding normal epithelial cells were observed. Furthermore, the relative increase of EMMPRIN was associated with a trend toward poor overall and recurrence‐free survival. High relative EMMPRIN expression was associated significantly with positive metastasis status (M1) (P = .001) and with a trend towards advanced pathologic tumor classification. Sixteen percent of disseminated tumor cells in bone marrow samples from patients with colorectal cancer and 48.5% of disseminated tumor cells in bone marrow samples from patients with gastric cancer stained positive for EMMPRIN, and EMMPRIN on micrometastatic cells was associated significantly with parameters of tumor progression (M status, noncurative resectability). A minority of normal bone marrow cells were stained for EMMPRIN, suggesting their suitability for molecular targeting. CONCLUSIONS: To the authors' knowledge, this study was the first to indicate that increased relative EMMPRIN protein in tumor‐specific cells compared with normal cells predicts poor disease‐specific survival in patients with colorectal cancer and that EMMPRIN in primary and bone marrow‐disseminated tumor cells is associated with clinical markers of tumor progression in patients with colorectal/gastric cancer. Cancer 2009. © 2009 American Cancer Society.

show abstract

Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer

Cited by 56 publications

References 12 publications

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis

TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118

Prognostic impact of extracellular matrix metalloprotease inducer

Contact Info

Product

Resources

About