Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth factor FGF3 in nude mice.
Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were constructed by the overlap-extension method. The proteins translated from two FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be the initiation codon, were shown to have the same molecular mass. This result suggests that translation of human FGF3, which is different from mouse FGF3, begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3 cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously into athymic nude mice. Nodular lesions developed at the injection sites in all seven mice injected with the F3-1 cell clone, which showed high expression of FGF3, and in two out of six mice injected with the F3-2 cell clone, which expressed a low level of FGF3. Histopathological features of these tumors contained fascicles of spindle-shaped cells surrounding irregular endothelial lined vascular clefts, similar to those observed in human KS lesions. Immunohistochemical staining for factor V111 antigen revealed reactivity in multiple areas, especially in abundant vascular structures of the tumor sections examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2, and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some similarities to human KS tumors. In conclusion, our results demonstrate the potential tumorigenic and angiogenic role of human FGF3.
Li
J J
JJ
Department of Microbiology and Medicine, NYU Medical Center, New York 10016, USA.
Friedman-Kien
A E
AE
Cockerell
C
C
Nicolaides
A
A
Liang
S L
SL
Huang
Y Q
YQ
D000818:Animals; D015152:Blotting, Northern; D015197:Carcinogenicity Tests; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors