Release of fibroblast growth factor-1 by human squamous cell carcinoma correlates with autocrine cell growth |
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Authors: | Yoshiko Myoken Yoshinari Myoken Tetsuji Okamoto Mikio Kan J Denry Sato Kazuaki Takada |
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Institution: | (1) Department of Oral and Maxillofacial Surgery 1, Hiroshima University School of Dentistry, 1-2-3 Kasumi, Minami-ku, 734 Hiroshima, Japan;(2) Center for Cancer Biology, Institute for Biosciences and Technology, Texas A and M University, 2121 W. Holcombe Blvd., 77030 Houston, Texas;(3) W. Alton Jones Cell Science Center, Inc., 10 Old Barn Road, 12946 Lake Placid, New York |
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Abstract: | A squamous cell carcinoma cell line Nakata proliferated in serum-free culture and was not responsive to exogenous fibroblast
growth factor-1 (FGF-1). Immunostaining revealed that Nakata cells expressed FGF-1 in their cytoplasms and nuclei. Two molecular
mass species of FGF-1 (16 and 18 kDa) were identified in cell extracts by Western blot. These cells also expressed high-affinity
FGF-1 binding sites (Kd=360 pM, 28 000 sites/cell). The results of cross-linking with 125I]FGF-1 demonstrated the presence of two bands with molecular masses of 160 and 140 kDa. The addition of FGF-1 specific antisense
oligonucleotides at 25 μM to Nakata cells resulted in an 82% inhibition in cell growth and suppressed FGF-1 expression. This effect was dose-dependent
and specific, because sense oligonucleotides were ineffective in inhibiting cell growth. In addition, Nakata cell growth was
suppressed by an anti-FGF-1 neutralizing antibody, which resulted in a 52% inhibition at 8 μg/ml. These results demonstrate
that Nakata cells produce FGF-1, and indicate that this growth factor acts in an autocrine manner by interacting with FGF-1
binding sites on Nakata cells. |
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Keywords: | autocrine growth fibroblast growth factor-1 serum-free culture squamous cell carcinoma |
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