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

Autor: Hitoo Nakano, Ayano Yamazaki, Eiji Oki, Hiroto Mizushima, Eisuke Mekada, Yoshihiro Tanaka, Shingo Miyamoto, Satoshi O. Suzuki, Kenzo Sonoda, Yoshihiko Maehara, Hiroshi Yagi
Rok vydání: 2005
Předmět:
EGF Family of Proteins
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
ADAM17 Protein
Amphiregulin
Disease-Free Survival
Epiregulin
Transactivation
chemistry.chemical_compound
Internal medicine
Lysophosphatidic acid
medicine
Disintegrin
Humans
RNA
Messenger
Epidermal growth factor receptor
Betacellulin
In Situ Hybridization
Glycoproteins
Ovarian Neoplasms
Metalloproteinase
Epidermal Growth Factor
biology
Reverse Transcriptase Polymerase Chain Reaction
Growth factor
Transforming Growth Factor alpha
Prognosis
medicine.disease
Immunohistochemistry
Gene Expression Regulation
Neoplastic
carbohydrates (lipids)
ADAM Proteins
Endocrinology
Oncology
chemistry
Disease Progression
biology.protein
Intercellular Signaling Peptides and Proteins
Female
Ovarian cancer
Heparin-binding EGF-like Growth Factor
Zdroj: Clinical Cancer Research. 11:4783-4792
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-04-1426
Popis: 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). ADAM 17 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 (γ = 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.
Databáze: OpenAIRE
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