Laminin 5 expression protects against anoikis at aerogenous spread and lepidic growth of human lung adenocarcinoma
| Autor: | Yoshiaki Hitomi, Takafumi Sangai, Shin'ichi Miyamoto, Takahiro Hasebe, Keiji Kodama, Masato Goya, Atsushi Ochiai, Takeshi Yoshikawa, Keisuke Izumi, Genichiro Ishii, Shi-chuan Zhang |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Integrins Lung Neoplasms Integrin Transplantation Heterologous Mice SCID Biology Adenocarcinoma Polymerase Chain Reaction Mice Cell Line Tumor medicine Adenocarcinoma of the lung Animals Humans Anoikis Epidermal growth factor receptor RNA Messenger DNA Primers A549 cell Cell adhesion molecule medicine.disease Flow Cytometry Immunohistochemistry Gene Expression Regulation Neoplastic Disease Models Animal Retroviridae Oncology Cell culture biology.protein Cancer research Laminin Cell Division |
| Zdroj: | International journal of cancer. 116(6) |
| ISSN: | 0020-7136 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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