NDLI: The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases.

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The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases.

Content Provider	Semantic Scholar
Author	Phillips, Roderick J. Burdick, Marie D. Lutz, Marin Belperio, John A. Keane, Michael P. Strieter, Robert M.
Copyright Year	2003
Abstract	Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for organ-specific metastasis is poorly understood, although evidence has suggested that the chemokine stromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 may regulate breast cancer metastasis. We hypothesized that the CXCL12-CXCR4 biological axis is important in mediating non-small cell lung cancer metastases. Our results indicate that both non-small cell lung cancer tumor specimens resected from patients and non-small cell lung cancer cell lines express CXCR4, but not CXCL12. Non-small cell lung cancer cell lines undergo chemotaxis in response to CXCL12. CXCL12-CXCR4 activation of non-small cell lung cancer cell lines showed intracellular calcium mobilization and mitogen-activated protein kinase activation with enhanced extracellular signal-related kinase-1/2 phosphorylation without change in either proliferation or apoptosis. Target organs in a murine model that are the preferred destination of human non-small cell lung cancer metastases elaborate higher levels of CXCL12 than does the primary tumor, and suggest the generation of chemotactic gradients. The administration of specific neutralizing anti-CXCL12 antibodies to severe combined immunodeficient mice expressing human non-small cell lung cancer abrogated organ metastases, without affecting primary tumor-derived angiogenesis. These data suggest that the CXCL12-CXCR4 biological axis is involved in regulating the metastasis of non-small cell lung cancer.
File Format	PDF HTM / HTML
DOI	10.1164/rccm.200301-071OC
Alternate Webpage(s)	https://cloudfront.escholarship.org/dist/prd/content/qt7tc7r69k/qt7tc7r69k.pdf
PubMed reference number	12626353
Alternate Webpage(s)	https://doi.org/10.1164/rccm.200301-071OC
Journal	Medline
Volume Number	167
Issue Number	12
Journal	American journal of respiratory and critical care medicine
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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