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Laminin 5 expression protects against anoikis at aerogenous spread and lepidic growth of human lung adenocarcinoma
Author(s) -
Kodama Keiji,
Ishii Gen'ichiro,
Miyamoto Shin'ichi,
Goya Masato,
Zhang Shichuan,
Sangai Takafumi,
Yoshikawa Takeshi,
Hasebe Takahiro,
Hitomi Yoshiaki,
Izumi Keisuke,
Ochiai Atsushi
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21136
Subject(s) - anoikis , biology , cancer research , integrin , a549 cell , protein kinase b , laminin , adenocarcinoma , epidermal growth factor receptor , microbiology and biotechnology , metastasis , signal transduction , receptor , cell culture , cancer , extracellular matrix , biochemistry , genetics
Abstract Adenocarcinoma of the lung is characterized by frequent aerogenous spread (AE) and advancement along the alveolar wall (BAC growth). To elucidate the mechanism of AE metastasis and BAC growth in human lung adenocarcinoma, we established an in vivo orthotopic animal model and an in vitro culture. Investigation of expression levels of integrins, laminins and Type IV collagens, which are the major regulating molecules for cell attachment and anoikis was carried out and a clear correlation between the expression level of laminin 5 (LN5) and the BAC growth was observed using an orthotopic animal model. Introduction of LN5 cDNA to A549 cells increased anoikis resistance in an expression dependent manner. Cells with LN5 overexpression resisted with anoikis after treatment with PI3K‐Akt and ERK inhibitors. The amount of phosphorylated focal adhesion kinase (FAK) was also higher in LN5 overexpressing cells. Major tyrosine residues of the EGF receptor at 1068, 1086 and 1173, except at 1148, remained phosphorylated only in the LN5 overexpressing cells even without EGF stimulation, that indicates the ligand independent activation of EGF receptor. BAC growth ratio and AE was confirmed to be significantly correlated with LN5 expression in surgically resected human lung adenocarcinomas by immunohistochemistry. Our results indicate that the activation of the EGF receptor by overexpressing LN5‐integrin‐FAK signaling pathway may play a crucial role in BAC growth and AE metastasis in human lung adenocarcinoma. © 2005 Wiley‐Liss, Inc.