Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma
Journal
Archives of Toxicology
Journal Volume
84
Journal Issue
8
Pages
651-660
Date Issued
2010
Author(s)
Abstract
Fibroblast growth factor (FGF)-9 belongs to the FGF family which modulate cell proliferation, differentiation, and motility. Benzo(a)pyrene is a polycyclic aromatic hydrocarbon (PAH) and ubiquitous environmental carcinogen present in automobile exhaust, cigarette smoke, and foods. The major purposes of this study were to explore the roles of FGF-9 in the benzo(a)pyrene-induced lung cancer invasion in vitro and the metastatic development of lung adenocarcinoma in human. The data of RT-PCR analysis indicated that treatments of human lung adenocarcinoma CL5 cells with benzo(a)pyrene and a PAH mixture motorcycle exhaust particulate (MEP) extracts increased FGF-9 mRNA expression. The increased expression was blocked by cotreatments with a p38 mitogen-activated protein kinase inhibitor SB202190 and an extracellular signal-regulated kinase inhibitor PD98059. The results of immunoblot analysis and Matrigel assay showed that benzo(a)pyrene and MEP extracts produced a concomitant induction of FGF-9 protein and invasive ability of CL5 cells. The benzo(a)pyrene- and MEP-induced invasion was suppressed by FGF-9 neutralizing antibodies. The results of immunohistochemistry analysis of human lung adenocarcinoma specimens showed that FGF-9 protein was detected in the adenocarcinoma cells but not in normal epithelium. FGF-9 staining intensity was positively correlated with status of disease and degree of lymph node metastasis in these lung adenocarcinomas. These present findings suggest that FGF-9 has potential roles in benzo(a)pyrene-induced CL5 cell invasion and human lung adenocarcinoma metastasis. ? 2010 Springer-Verlag.
SDGs
Other Subjects
2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 hydroxyphenyl) 5 (4 pyridyl)imidazole; benzo[a]pyrene; fibroblast growth factor 9; mitogen activated protein kinase; mitogen activated protein kinase p38; neutralizing antibody; polycyclic aromatic hydrocarbon; adult; article; cancer growth; cancer inhibition; cancer invasion; controlled study; exhaust gas; female; gene expression regulation; human; human cell; human tissue; immunoblotting; immunohistochemistry; in vitro study; lung adenocarcinoma; lymph node metastasis; major clinical study; male; metastasis; particulate matter; priority journal; protein analysis; protein function; protein induction; reverse transcription polymerase chain reaction; Adenocarcinoma; Adult; Aged; Benzo(a)pyrene; Carcinogens, Environmental; Female; Fibroblast Growth Factor 9; Humans; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness
Type
journal article