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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Introduction of basic fibroblast growth factor gene into mouse renal cell carcinoma cell line enhances its metastatic
H Miyake1, I Hara, K Yoshimura
1Department of Urology, Kobe University School of Medicine, Japan.
Abstract:
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.
Insights
Basic fibroblast growth factor (FGF-2) overexpression enhances renal cell carcinoma invasion and metastasis, likely by increasing matrix metalloproteinase 2 (MMP-2) production. This study clarifies FGF-2
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Renal cell carcinoma (RCC) is a significant health concern.
- The role of basic fibroblast growth factor (FGF-2) in RCC malignancy is not fully understood.
Purpose of the Study:
- To investigate the specific role of endogenous FGF-2 in the malignant progression of renal cell carcinoma.
- To determine if FGF-2 influences invasion, metastasis, and matrix metalloproteinase production in RCC.
Main Methods:
- Transfection of the FGF-2 gene into a mouse RCC cell line (RenCa).
- In vitro invasion assays and zymography to assess invasiveness and MMP-2 production.
- In vivo studies involving intravenous and subcapsular injection in syngeneic mice to evaluate metastatic potential.
Main Results:
- FGF-2-transfected cells showed a 3- to 4-fold increase in invasive potential in vitro.
- Elevated matrix metalloproteinase 2 (MMP-2) production was observed in FGF-2-transfected cells.
- FGF-2 overexpression led to a >10-fold increase in lung metastases and additional metastases to the liver and lymph nodes in vivo.
- No significant differences in cell proliferation or tumor growth were observed.
Conclusions:
- Endogenous FGF-2 plays a critical role in the invasion and metastasis of renal cell carcinoma.
- FGF-2 likely promotes RCC malignancy through the upregulation of MMP-2 production.
- Targeting FGF-2 may offer a therapeutic strategy for advanced renal cell carcinoma.
