FGF1 and FGF2 in Tumor Development

Extensive studies on the expression of FGF-1 and FGF-2 in tumor biopsies in vivo together with functional studies on tumor cell proliferation in vitro, provided a plethora of evidence for the involvement of FGF-1 and FGF-2 in tumor development. In some cases, expression of FGF-1 or FGF-2 correlated with malignancy, and interference with the activities of FGF-1 or FGF-2 diminished tumor growth and cell transformation (15). FGF-1 and FGF-2 were significantly upregulated in human gliomas, proportional with the degree of malignancy (15). Furthermore, the malignant phenotype of glioblas-toma cell lines could be inhibited by FGF-2-specific antibodies, indicating that FGF-2 utilized an autocrine pathway to promote tumor progression (16). FGF-2 and sometimes FGF-1 are constitutively expressed at high levels in melanomas, but not in normal melanocytes (8). Proliferation and growth in soft agar was inhibited by antisense oligonucleotides to FGF-2 or FGFR-1 in melanoma cell line, indicating that FGF-2 might be a major autocrine growth factor for melanoma cells (17). In Kaposi's sarcoma (KS), FGF-2 and sometimes FGF-1 were detectable in tissue specimen and KS-derived cell lines. In fact, proliferation, angiogenesis, and lesion formation by KS-derived cell lines in athymic mice could be prevented by treatment with antisense oligonucleotides to FGF-2 (18).

Elevated expression of either FGF-1 or FGF-2 has been demonstrated in a variety of other tumor types in vivo, and in tumor cell lines in vitro. In some cases, FGF expression correlated significantly with advanced stages of tumor development and malignancy (reviewed in refs. 1 and 2). Examples include the expression of FGF-2 and FGF-1 in squamous cell carcinoma, human leukemic cells, human bladder carcinoma, human pancreatic carcinoma, human ovarian cancer, and gastric carcinoma; and the expression of FGF-2 in pituitary tumors, renal tumors, mammary carcinoma cell lines, prostate carcinoma cell lines, colon carcinoma cell lines, hepatoma cell lines, chondrosarcoma cell lines, osteosarcoma cell lines, and the expression of FGF-1 in rat Morris hepatoma cell lines (19).

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