Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic potential.
To clarify the role of basic fibroblast growth factor (FGF-2) in the malignant progression of renal cell carcinoma, we transfected the FGF-2 gene, which lacks the typical signal sequence, into RenCa, a mouse renal cell carcinoma cell line that does not express FGF-2 mRNA. In an in vitro tumor cell invasion assay, the FGF-2-transfected cell lines (RenCa/F) exhibited 3- to 4-fold higher invasive potential than either the parental RenCa (RenCa/P) or the vector-only transfected cell line (RenCa/C). Zymography showed a marked increase in matrix metalloproteinase 2 (MMP-2) production in the culture supernatants of RenCa/F. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa/F formed more than 10 times as many metastatic nodules in the lung as did RenCa/P and RenCa/C. Metastases to the liver and mesenteric lymph nodes were observed only after the injection of RenCa/F into the renal subcapsule. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among RenCa sublines. These results suggest that if it is overexpressed, endogenous native FGF-2 plays an important role in the invasion and metastasis of renal cell carcinoma, probably through the production of MMP-2.
Miyake
H
H
Department of Urology, Kobe University School of Medicine, Japan.
Hara
I
I
Yoshimura
K
K
Eto
H
H
Arakawa
S
S
Wada
S
S
Chihara
K
K
Kamidono
S
S
D000818:Animals; D001483:Base Sequence; D001485:Basement Membrane; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D003094:Collagen; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D007797:Laminin; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013370:Subrenal Capsule Assay; D014162:Transfection; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2