Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-C.
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.
Ramos
D M
DM
Department of Stomatology, UCSF, San Francisco, CA 94143-0512, USA. dramos@itsa.ucsf.edu
Chen
B L
BL
Boylen
K
K
Stern
M
M
Kramer
R H
RH
Sheppard
D
D
Nishimura
S L
SL
Greenspan
D
D
Zardi
L
L
Pytela
R
R
D000818:Animals; D000951:Antigens, Neoplasm; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D019063:Tenascin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D017077:Culture Media, Conditioned; D016023:Integrins; D019063:Tenascin; C073878:integrin alphavbeta6