Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C

Int J Cancer. 1997 Jul 17;72(2):369-76. doi: 10.1002/(sici)1097-0215(19970717)72:2<369::aid-ijc28>;2-9.


In this study we identified tenascin-C (TN-C) and one of its integrin receptors, alpha(v)beta6, in oral squamous-cell carcinoma (SCC) specimens. Neither TN-C nor alpha(v)beta6 are expressed in normal oral mucosa. We also studied 2 human oral squamous-cell carcinoma cell lines: the highly invasive HSC-3 cells, and the poorly invasive SCC-25 cells. We determined that adhesion of these cells to TN-C involves both alpha2 and alpha(v) integrins. Migration on TN-C by oral SCC cells required fibroblast-conditioned medium and did not occur in its absence. This migration was blocked by anti-alpha2 and anti-alpha(v) antibodies and was partially inhibited by antibodies to hepatocyte growth factor, epidermal growth factor and transforming growth factor-beta1. When seeded on TN-C, the poorly invasive SCC-25 cells formed alpha(v)beta6-positive focal contacts; the HSC-3 cells did not. HSC-3, SCC-25 and PTF cells secrete TN-C into the culture medium, as determined by Western blot. However, when HSC-3 cells were inoculated into the floor of the mouth of nude mice, only murine TN-C could be identified in the reactive stroma adjacent to the resulting tumor nests, demonstrating that in vivo, HSC-3 cells do not secrete TN-C. Our results demonstrate that alpha(v)beta6 and tenascin-C are neo-expressed in oral squamous-cell carcinoma, and that the tumor stromal environment is influential in oral SCC behavior.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion
  • Cell Movement
  • Culture Media, Conditioned
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Integrins / metabolism
  • Mice
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Tenascin / metabolism*
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Culture Media, Conditioned
  • Integrins
  • Tenascin
  • integrin alphavbeta6