|Title:||Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma||Authors:||Chao Y.-C.
|Issue Date:||2009||Journal Volume:||179||Journal Issue:||2||Start page/Pages:||123-133||Source:||American Journal of Respiratory and Critical Care Medicine||Abstract:||
Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. Objectives: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression. Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-α], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor. Conclusions: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.
|ISSN:||1073-449X||DOI:||10.1164/rccm.200803-456OC||SDG/Keyword:||claudin 1; messenger RNA; adult; aged; animal experiment; animal model; animal tissue; article; cancer cell; cancer invasion; cell migration; controlled study; female; gene identification; gene overexpression; histopathology; human; human cell; human tissue; immunohistochemistry; lung adenocarcinoma; major clinical study; male; metastasis; microarray analysis; mouse; nonhuman; outcome assessment; priority journal; protein expression; protein function; protein localization; real time polymerase chain reaction; reverse transcription polymerase chain reaction; Adenocarcinoma; Aged; Cohort Studies; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Analysis; Tumor Markers, Biological
|Appears in Collections:||病理學科所|
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