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

Int J Cancer. 1999 Sep 24;83(1):38-44. doi: 10.1002/(sici)1097-0215(19990924)83:1<38::aid-ijc8>;2-b.


Bone morphogenetic proteins (BMPs) are multifunctional cytokines. BMP-6 is involved in early steps of keratinogenesis. Esophageal squamous-cell carcinoma often shows abnormal keratinization. The aim of this study was to examine the expression and regulation of BMP-6 in esophageal carcinoma and to determine the relationship of its expression with tumor characteristics and survival. Avidin-biotin-peroxidase staining was performed using paraffin-wax-embedded tumor specimens collected from 172 patients with esophageal squamous-cell carcinoma, who underwent potentially curative surgery. Expression of BMP-6 and EGF-receptor in the esophageal-squamous-cell-carcinoma cell line 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 serum-free conditions BMP-6 expression was hardly detectable. The addition of EGF or EGF-related growth factors could elevate BMP-6 mRNA content. Immunohistochemically, all 172 tumors exhibited cytoplasmic immunoreactivity for BMP-6. The content of BMP-6 protein was inversely correlated with tumor differentiation (p < 0.01). Univariate survival analysis revealed that 74 patients with tumors of low immunoreactivity had higher 2-year and 5-year survival 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 the grade of tumor-cell differentiation and may add to indications of poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Culture Media, Serum-Free
  • ErbB Receptors / metabolism
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypopharyngeal Neoplasms / metabolism
  • Immunohistochemistry
  • Keratinocytes / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Time Factors
  • Tumor Cells, Cultured


  • BMP6 protein, human
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • Culture Media, Serum-Free
  • ErbB Receptors