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
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.