Expression, regulation and clinical significance of bone morphogenetic protein 6 in esophageal squamous-cell carcinoma

Citation
M. Raida et al., Expression, regulation and clinical significance of bone morphogenetic protein 6 in esophageal squamous-cell carcinoma, INT J CANC, 83(1), 1999, pp. 38-44
Citations number
31
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
00207136 → ACNP
Volume
83
Issue
1
Year of publication
1999
Pages
38 - 44
Database
ISI
SICI code
0020-7136(19990924)83:1<38:ERACSO>2.0.ZU;2-E
Abstract
Bone morphogenetic proteins (BMPs) are multifunctional cytokines, BMP-6 is involved in early steps of keratinogenesis, Esophageal squamous cell carcin oma often shows abnormal keratinization, The aim of this study was to exami ne the expression and regulation of BMP-6 in esophageal carcinoma and to de termine the relationship of its expression with tumor characteristics and s urvival. Avidin-biotin-peroxidase staining was performed using paraffin-wax -embedded tumor specimens collected from 172 patients with esophageal squam ous-cell carcinoma, who underwent potentially curative surgery. Expression of BMP-6 and EGF-receptor in the esophageal-squamous cell carcinoma cell li ne COLO-680N and the hypopharyngeal-squamous cell carcinoma cell line FaDu was assayed with specific RT-PCR, In standard cell-cultivation conditions, COLO-680N and FaDu cells showed distinct expression of BMP-6, whereas in se rum-free conditions BMP-6 expression was hardly detectable. The addition of EGF or EGF-related growth factors could elevate BMP-6 mRNA content. Immuno histochemically, all 172 tumors exhibited cytoplasmic immunoreactivity for BMP-6. The content of BMP-6 protein was inversely correlated with tumor dif ferentiation (p < 0.01). Univariate survival analysis revealed that 74 pati ents with tumors of low immunoreactivity had higher 2-year and 5-year survi val rates (50.0%/27.7%) than 75 patients with tumors of high immunoreactive scores (33.3%/ 21.6%). (p < 0.05). We conclude that BMP-6 is expressed in esophageal squamous-cell carcinoma, EGF-receptor activation is crucial for regulation of BMP-6 expression. BMP-6 protein content is correlated with th e grade of tumor-cell differentiation and may add to indications of poor pr ognosis. (C) 1999 Wiley-Liss, Inc.