通过阻断原始和骨转移性肾细胞癌中的FGF-2抑制血管生成。
Inhibition of angiogenesis via FGF-2 blockage in primitive and bone metastatic renal cell carcinoma.
作者信息
Cenni Elisabetta, Perut Francesca, Granchi Donatella, Avnet Sofia, Amato Ilaria, Brandi Maria Luisa, Giunti Armando, Baldini Nicola
机构信息
Laboratory for Pathophysiology of Orthopedic Implants, Istituti Ortopedici Rizzoli, Bologna, Italy.
出版信息
Anticancer Res. 2007 Jan-Feb;27(1A):315-9.
BACKGROUND
Fibroblast growth factor-2 (FGF-2) has a role in the angiogenesis induced by renal carcinoma.
MATERIALS AND METHODS
Blockage of FGF-2 by an antisense oligonucleotide (ASO) or by a mouse neutralizing anti-human FGF-2 monoclonal antibody (anti-FGF-2-mAb) was evaluated on a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990), on Caki-1 and ACHN cells. Cocultures of endothelial cells and ASO- or mAb-treated carcinoma lines were investigated.
RESULTS
Anti-FGF-2-mAb treatment induced a 33% reduction of FGF-2 released by ACHN, a 31% reduction of FGF-2 released by Caki-1, and a 70% reduction of FGF-2 released by CRBM-1990. ASO treatment did not inhibit endothelial cell proliferation. In contrast, anti-FGF-2-mAb significantly decreased endothelial cells proliferation induced by ACHN and CRBM-1990. The inhibition of endothelial cell growth was reverted by recombinant FGF-2.
CONCLUSION
Modulation of FGF-2 production by renal cell carcinoma with a blocking mAb produced a significant inhibition of endothelial cell growth.
背景
成纤维细胞生长因子-2（FGF-2）在肾癌诱导的血管生成中起作用。
材料与方法
在从肾癌骨转移分离的细胞系（CRBM-1990）、Caki-1细胞和ACHN细胞上评估反义寡核苷酸（ASO）或小鼠中和抗人FGF-2单克隆抗体（抗FGF-2-mAb）对FGF-2的阻断作用。研究了内皮细胞与经ASO或mAb处理的癌细胞系的共培养。
结果
抗FGF-2-mAb处理使ACHN释放的FGF-2减少33%，Caki-1释放的FGF-2减少31%，CRBM-1990释放的FGF-2减少70%。ASO处理未抑制内皮细胞增殖。相反，抗FGF-2-mAb显著降低了ACHN和CRBM-1990诱导的内皮细胞增殖。重组FGF-2可逆转内皮细胞生长的抑制。
结论
用阻断性单克隆抗体调节肾细胞癌中FGF-2的产生可显著抑制内皮细胞生长。
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