Fibroblast growth factor-2 expression during experimental oral carcinogenesis. Its possible role in the induction of pre-malignant fibrosis.
BACKGROUND
The fibroblastic growth factor (FGF)-2 has been shown to induce angiogenesis in several tumor types. To date, the activity of FGF during the development of oral pre-cancerous lesions has not been analyzed. We herein evaluated the role of FGF-2 in the pre-cancerous and cancerous lesions in the hamster cheek pouch oral cancer model.


METHODS
Expression of FGF-2 and its receptors FGFR-2 and FGFR-3 was assessed by immunohistochemistry at different stages of the carcinogenesis protocol. Activity of FGF-2 isoforms was analyzed by Western blots.


RESULTS
Increase and abnormal localization of FGF-2 expression was evident in cancerized epithelium before it was possible to detect morphologic alterations. The changes in FGF-2 are concomitant with the evolution of subepithelial fibrosis. Immunolabeling of carcinomas was faint or completely negative. Increases of FGF-2 activity are mainly due to the increase in the 18 kDa isoform. Receptors 2 and 3 of FGF are present in epithelium, fibroblasts, and vascular endothelia of control samples and in all stages of malignant transformation.


CONCLUSIONS
Our results would suggest a role for FGF-2 in the epithelium-connective interactions and a deregulation of its expression in the early stages of oral cancerization. In pre-cancerous tissue FGF-2 would play a central role in the development of fibrosis and a more collateral role in the induction of angiogenesis. The data would indicate its involvement in the process via the 18 kDa isoform.
Raimondi
A R
AR
Oral Pathology Department, Faculty of Dentistry, University of Buenos Aires, Argentina.
Molinolo
A A
AA
Itoiz
M E
ME
D000818:Animals; D015153:Blotting, Western; D002610:Cheek; D006224:Cricetinae; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D005355:Fibrosis / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics; D011230:Precancerous Conditions / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis / Q000235:genetics
D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3