Detection of Circulating Basic Fibroblast Growth Factor (bFGF) in Serum of Animals with Known Malignancy: A Pilot Study of Felids and Ursids
Angiogenesis, new blood vessel growth, is a critical step in the growth and metastasis of solid tumors.1 Basic fibroblast growth factor (bFGF) is a potent angiogenic cytokine expressed by tumors, and is present at elevated levels in the serum of human cancer patients, and it correlates to prognosis and survival.2-6 Because bFGF has a highly conserved homology across species, we hypothesized that felids and sloth bears, both highly prone to malignancies, would also demonstrate bFGF levels in their serum as an indicator of cancer. The purpose of this study was to determine if bFGF is detectable in felids and ursids, and correlative with malignancy.
We examined serum samples from 15 animals (4 Siberian tigers [Panthera tigris altaica], 2 Persian leopards [Panthera pardus saxicolor], 1 Indian leopard [Panthera pardus], 1 snow leopard [Panthera uncia], 1 jaguar [Panthera onca], 1 African lion [Panthera leo], 3 sloth bears [Melursus ursinus], and 2 domestic cats [Felis catus]). Four of the animals had known malignancy (uterine leiomyosarcoma (1 Indian leopard); bronchoalveolar carcinoma (1 African lion); metastatic adenocarcinoma of the liver (1 sloth bear); vaccine-related fibrosarcoma (1 domestic cat). Eleven healthy animals served as controls. An ELISA assay (Quantikine, R&D Systems, Minneapolis, Minnesota USA) was used to quantitate serum bFGF levels.
Basic FF levels were detected in three of four animals with known malignancy (African lion=8.98 pg/ml; sloth bear=21.0 pg/ml; domestic cat=35.46 pg/ml). No bFGF was detected in 9 of 11 healthy control animals. Two animals thought to be healthy had detectable bFGF (Siberian tiger=71.29 pg/ml; snow leopard=2.27 pg/ml) and were later diagnosed with metastatic mammary adenocarcinoma and soft tissue sarcoma respectively. At a 12-mo follow-up, all truly healthy animals remained alive and without evidence of cancer.
In this pilot study, the angiogenic cytokine, bFGF, was detectable in the serum of felids and sloth bears with a variety of malignancies. In contrast, animals without neoplasms did not have detectable bFGF in their serum. Further studies are warranted to determine if bFGF may serve as a biologic marker for malignancy for possible application in: 1) early cancer detection; 2) disease prognosis; and 3) selection of novel antiangiogenic therapeutics for the treatment of cancers of felids, ursids, and other animals.
1. Folkman J. 1995. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Medicine. 1:27–31.
2. Meyer GE, E Yu, JA Siegal, JC Petteway, BA Blumenstein, MK Brawer. 1995. Serum basic fibroblast growth factor in men with and without prostate carcinoma. Cancer. 76:2304–11.
3. Sliutz G, C Tempfer, A Obermair, A Reinthaller, G Gitsch, Ch. Kainz. 1995. Serum evaluation of basic fibroblast growth factor in cervical cancer patients. Cancer Letters. 94:227–31.
4. Nyugen M, H Watanabe, AE Budson, JP Richie, DF Hayes, J Folkman. 1994. Elevated levels of an angiogenic peptide, basic fibroblast growth factor in the urine of patients with a wide spectrum of cancers. J Nat Cancer Inst. 86:356–61.
5. Watanabe H, M Nguyen, M Schizer, V Li, DF Hayes, S Sallan, J Folkman. 1992. Basic fibroblast growth factor in human serum: a prognostic test for breast cancer. Molec Biol Of the Cell. 3:234a.
6. Li VW, RD Folkerth, H Watanabe, C Yu, M Rupnick, P Barcus, RM Scott, PMcL. Black, SR Sallan, J Folkman. 1994. Basic fibroblast growth factor in the cerebrospinal fluid of children with brain tumours - correlation with microvessel count in the tumor. Lancet. 344:82–86.