Format

Send to

Choose Destination
Clin Cancer Res. 2009 Nov 15;15(22):6820-9. doi: 10.1158/1078-0432.CCR-09-1558. Epub 2009 Nov 3.

Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma.

Author information

1
Lung Cancer Research Program, Division of Pulmonary and Critical Care Medicine, 10833 Le Conte Avenue, 37-131 CHS, Los Angeles, CA 90095-1690, USA.

Abstract

PURPOSE:

As a transcriptional repressor of E-cadherin, Snail has predominantly been associated with epithelial-mesenchymal transition, invasion, and metastasis. However, other important Snail-dependent malignant phenotypes have not been fully explored. Here, we investigate the contributions of Snail to the progression of non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN:

Immunohistochemistry was done to quantify and localize Snail in human lung cancer tissues, and tissue microarray analysis was used to correlate these findings with survival. NSCLC cell lines gene-modified to stably overexpress Snail were evaluated in vivo in two severe combined immunodeficiency murine tumor models. Differential gene expression between Snail-overexpressing and control cell lines was evaluated using gene expression microarray analysis.

RESULTS:

Snail is upregulated in human NSCLC tissue, and high levels of Snail expression correlate with decreased survival (P < 0.026). In a heterotopic model, mice bearing Snail-overexpressing tumors developed increased primary tumor burden (P = 0.008). In an orthotopic model, mice bearing Snail-overexpressing tumors also showed a trend toward increased metastases. In addition, Snail overexpression led to increased angiogenesis in primary tumors as measured by MECA-32 (P < 0.05) positivity and CXCL8 (P = 0.002) and CXCL5 (P = 0.0003) concentrations in tumor homogenates. Demonstrating the importance of these proangiogenic chemokines, the Snail-mediated increase in tumor burden was abrogated with CXCR2 blockade. Gene expression analysis also revealed Snail-associated differential gene expression with the potential to affect angiogenesis and diverse aspects of lung cancer progression.

CONCLUSION:

Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands.

PMID:
19887480
PMCID:
PMC2783274
DOI:
10.1158/1078-0432.CCR-09-1558
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center