ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

Grützmann, Robert; Lüttges, Jutta; Sipos, Bence; Ammerpohl, Ole; Dobrowolski, F.; Alldinger, Ingo; Kersting, Stephan; Ockert, D.; Koch, Rainer; Kalthoff, Holger; Schackert, H. K.; Saeger, Hans‐Detlev; Klöppel, G.; Pilarsky, Christian

doi:10.1038/sj.bjc.6601645

Cited by 120 publications

(91 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…of ADAM9 in non-small cell lung cancer has been correlated with brain metastases (24); furthermore, ADAM9 expression in pancreatic cancer has been suggested to be a prognostic factor in ductal adenocarcinoma (51). However, our studies, for the first time, point to the stromal component of an invasive tumor as the source of ADAM9 expression and thus suggest a functional role for stroma-derived ADAM9 in the context of local invasion of metastatic cancer cells.…”

Section: Discussioncontrasting

confidence: 39%

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

et al. 2005

View full text Add to dashboard Cite

Tumor cell invasion is a process regulated by integrins, matrix-degrading enzymes, and interactions with host tissue stromal cells. The ADAM family of proteins plays an important role in modulating various cellular responses. Here, we show that an alternatively spliced variant of ADAM9 is secreted by hepatic stellate cells and promotes carcinoma invasion. ADAM9-S induced a highly invasive phenotype in several human tumor cell lines in Matrigel assays, and the protease activity of ADAM9-S was required for invasion. ADAM9-S binds directly to A 6 B 4 and A 2 B 1 integrins on the surface of colon carcinoma cells through the disintegrin domain. ADAM9-S was also able to cleave laminin and promote invasion. Analysis of human liver metastases revealed that ADAM9 is expressed by stromal liver myofibroblasts, particularly those that are localized within the tumor stroma at the invasive front. These results emphasize the importance of tumor-stromal interactions in invasion and suggest that ADAM9-S can be an important determinant in the ability of cancer cells to invade and colonize the liver. (Cancer Res 2005; 65(11): 4728-38)

show abstract

Section: Discussioncontrasting

confidence: 39%

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In particular, recent findings have revealed that the ADAM family is involved in cancer. ADAM 9 expression is associated with the clinical significance of human breast and pancreatic cancers (40,41), whereas abundant ADAM 17 protein is expressed in human breast cancer (42). In human gastric carcinoma, high levels of transcripts for ADAM 10, 17, and 20 are present (43), whereas, in human liver cancer, expression of ADAM 9 and 12 is associated with tumor aggressiveness and progression (44).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Heparin-Binding Epidermal Growth Factor–Like Growth Factor and A Disintegrin and Metalloprotease 17 Expression in Human Ovarian Cancer

Tanaka

Miyamoto

Suzuki

et al. 2005

Clinical Cancer Research

144

121

View full text Add to dashboard Cite

Purpose: Lysophosphatidic acid, which is enriched in the peritoneal fluid of ovarian cancer patients, plays a key role in the progression of ovarian cancer. Lysophosphatidic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases. We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphatidic acid^induced pathogenesis of ovarian cancer. Experimental Design: We examined the expression of EGFR ligands and ADAM family members in 108 patients with normal ovaries or ovarian cancer, using real-time PCR, immunohistochemistry, and in situ hybridization, and analyzed the clinical roles of these molecules. Statistical analyses of these data were done using the Mann-Whitney test, Kaplan-Meier method, or Spearman's correlation analysis. Results: Large differences in expression were found for heparin-binding EGF-like growth factor (HB-EGF) and other EGFR ligands and for ADAM 17 and other ADAM family members. HB-EGF expression was significantly increased in advanced ovarian cancer compared with that in normal ovaries (P < 0.01). HB-EGF expression was significantly associated with the clinical outcome (P < 0.01). ADAM17 expression was significantly enhanced in both early and advanced ovarian cancer compared with that in normal ovaries (both P < 0.01), although it had no clinical significance in the progression-free survival. HB-EGF expression was significantly correlated with ADAM 17 expression (c = 0.437, P < 0.01).Conclusions: Our findings suggest that HB-EGF and ADAM 17 contribute to the progression of ovarian cancer and that HB-EGF plays a pivotal role in the aggressive behavior of a tumor in ovarian cancer.

show abstract

“…This study was initiated because the membrane anchored metalloprotease-disintegrin ADAM9 is highly expressed in several human carcinomas (3)(4)(5)(6). We found that ADAM9 is also prominently expressed in epithelial cells undergoing neoplastic changes in mouse models for prostate, breast, and intestinal cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, overexpression of ADAM9 has been reported in several human carcinomas, including breast (3), liver (4,5), pancreas (6), and gastric cancer (7). The goal of this study was to address whether ADAM9 might play a causative role in tumor development.…”

Section: Introductionmentioning

confidence: 99%

Critical Function for ADAM9 in Mouse Prostate Cancer

Reuter²,

et al. 2005

View full text Add to dashboard Cite

ADAM9 is a membrane-anchored metalloprotease that is markedly up-regulated in several human carcinomas. Here, we show that ADAM9 is similarly up-regulated in mouse models for prostate, breast, and intestinal carcinoma. To assess whether ADAM9 is critical for the pathogenesis of prostate carcinoma, one of the most common cancers in men, we evaluated how loss of ADAM9 affects tumorigenesis in W 10 mice, a mouse model for this disease. In the absence of ADAM9, most tumors in 50-week-old W 10 mice were well differentiated, whereas littermate controls expressing wild-type ADAM9 had predominantly poorly differentiated, and in some cases significantly larger, tumors. Moreover, gain-of-function experiments in which ADAM9 was overexpressed in mouse prostate epithelium resulted in significant abnormalities, including epithelial hyperplasia at 4 to 6 months of age, and prostatic intraepithelial neoplasia after 1 year. A potential underlying mechanism for the role of ADAM9 in prostate cancer emerged from cell-based assays: ADAM9 can cleave and release epidermal growth factor and FGFR2iiib from cells, both of which have pivotal functions in the pathogenesis of this disease. Taken together, these results suggest that ADAM9 contributes to the pathogenesis of prostate cancer and potentially also other carcinomas, raising the possibility that ADAM9 might be a good target for antitumor drugs. (Cancer Res 2005; 65(20): 9312-9)

show abstract

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

Cited by 120 publications

References 19 publications

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

A Secreted Form of ADAM9 Promotes Carcinoma Invasion through Tumor-Stromal Interactions

Clinical Significance of Heparin-Binding Epidermal Growth Factor–Like Growth Factor and A Disintegrin and Metalloprotease 17 Expression in Human Ovarian Cancer

Critical Function for ADAM9 in Mouse Prostate Cancer

Contact Info

Product

Resources

About