Mydlo J H, Kral J G, Macchia R J
Department of Urology, State University of New York Health Science Center at Brooklyn 11203, USA.
Urology. 1997 Sep;50(3):472-8. doi: 10.1016/S0090-4295(97)00265-3.
Basic fibroblast growth factor (bFGF or FGF-2) is mitogenic to human prostate epithelial and stromal cells, and it is reported to be elevated in the serum and urine of patients with various cancers, including prostate cancer. Obesity, with increased body fat, is a risk factor for prostate cancer through unknown mechanisms. Because adipose tissue is a source of FGF-2, we determined the quantity and quality of activity of FGF-2 in omental adipose tissue and compared it with normal and cancerous prostate tissues.
Using heparin-Sepharose chromatography, we extracted proteins from human omental adipose tissue, adenocarcinoma of the prostate, and benign prostatic hypertrophic (BPH) tissues. Each of the mitogenic proteins eluted with NaCl concentrations between 1.4 M and 1.8 M, similar to control FGF-2. Using FGF-2 antisera (which inhibited the mitogenic activity of the proteins), we performed Western blot analysis to confirm their homology to FGF-2. We also assessed recovery, mitogenicity, and angiogenicity of each of the proteins using thymidine incorporation into human umbilical vein endothelial cells and the chorioallantoic membrane assay.
There was greater recovery of FGF-2 from omental adipose tissue compared with cancerous or BPH homogenates (40 micrograms [2.0 micrograms/g] versus 25 micrograms [1.25 micrograms/g] and 20 micrograms [1.0 microgram/g], respectively). Moreover. FGF-2 from adipose tissue had greater mitogenic activity (96.2% versus 74.8% and 54%; P < 0.05) and a greater angiogenic activity (5.1 vessels versus 2.9 and 1.8 vessels; P < 0.05) on the chorioallantoic assay.
We suggest that human omental adipose tissue FGF-2 may demonstrate greater mitogenic and angiogenic activity than either BPH or prostate cancer tissue FGF-2. It is not known whether FGF-2 from adipose tissue qualitatively or quantitatively may underlie the relationship between obesity and prostate cancer.
碱性成纤维细胞生长因子(bFGF或FGF-2)对人前列腺上皮细胞和基质细胞具有促有丝分裂作用,据报道,在包括前列腺癌在内的各种癌症患者的血清和尿液中其水平会升高。肥胖导致体内脂肪增加,通过未知机制成为前列腺癌的一个危险因素。由于脂肪组织是FGF-2的一个来源,我们测定了网膜脂肪组织中FGF-2的活性数量和质量,并将其与正常和癌性前列腺组织进行比较。
我们使用肝素-琼脂糖色谱法从人网膜脂肪组织、前列腺腺癌组织和良性前列腺增生(BPH)组织中提取蛋白质。每种促有丝分裂蛋白均在1.4 M至1.8 M的氯化钠浓度下洗脱,这与对照FGF-2相似。我们使用FGF-2抗血清(可抑制这些蛋白质的促有丝分裂活性)进行蛋白质免疫印迹分析,以确认它们与FGF-2的同源性。我们还通过将胸苷掺入人脐静脉内皮细胞以及采用尿囊绒膜试验来评估每种蛋白质的回收率、促有丝分裂活性和血管生成活性。
与癌性或BPH匀浆相比,从网膜脂肪组织中回收的FGF-2更多(分别为40微克[2.0微克/克],而癌性组织为25微克[1.25微克/克],BPH组织为20微克[1.0微克/克])。此外,脂肪组织中的FGF-2在尿囊绒膜试验中具有更强的促有丝分裂活性(96.2%,而癌性组织为74.8%,BPH组织为54%;P<0.05)和更强的血管生成活性(5.1条血管,而癌性组织为2.9条,BPH组织为1.8条血管;P<0.05)。
我们认为,人网膜脂肪组织中的FGF-2可能比BPH或前列腺癌组织中的FGF-2表现出更强的促有丝分裂和血管生成活性。目前尚不清楚脂肪组织中的FGF-2在质量或数量上是否可能是肥胖与前列腺癌之间关系的基础。