Linked Life Data

21056990

Source:http://linkedlifedata.com/resource/pubmed/id/21056990

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2010-12-16
pubmed:abstractText
Highly metastatic and chemotherapy-resistant properties of malignant melanomas stand as challenging barriers to successful treatment; yet, the mechanisms responsible for their aggressive characteristics are not fully defined. We show that a distinct population expressing CD133 (Prominin-1), which is highly enriched after administration of a chemotherapeutic drug, dacarbazine, has enhanced metastatic potential in vivo. CD133(+) tumor cells are located close to tumor-associated lymphatic vessels in metastatic organs such as the regional lymph nodes and lung. Lymphatic endothelial cells promote the migratory activity of a CD133(+) subset to target organs and regulation of lymphatic growth efficiently modulates the metastasis of CD133(+) tumor cells. We found that lymphatic vessels in metastatic tissues stimulate chemokine receptor 4 (CXCR4)(+)/CD133(+) cell metastasis to target organs by secretion of stromal cell-derived factor-1 (SDF-1). The CXCR4(+)/CD133(+) cells exhibited higher metastatic activity compared with CXCR4(-)/CD133(+) cells and, importantly, blockade of CXCR4 coupled with dacarbazine efficiently inhibited both tumor growth and metastasis; dacarbazine alone could not attenuate tumor metastasis. The current study demonstrates a previously unidentified role of the lymphatic microenvironment in facilitating metastasis of chemoresistant melanoma cells via a specific chemotactic axis, SDF-1/CXCR4. Our findings suggest that targeting the SDF-1/CXCR4 axis in addition to dacarbazine treatment could therapeutically block chemoresistant CD133(+) cell metastasis toward a lymphatic metastatic niche.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
©2010 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10411-21
pubmed:meshHeading
pubmed-meshheading:21056990-Animals, pubmed-meshheading:21056990-Antigens, CD, pubmed-meshheading:21056990-Cell Movement, pubmed-meshheading:21056990-Chemokine CXCL12, pubmed-meshheading:21056990-Dacarbazine, pubmed-meshheading:21056990-Drug Resistance, Neoplasm, pubmed-meshheading:21056990-Endothelial Cells, pubmed-meshheading:21056990-Glycoproteins, pubmed-meshheading:21056990-Heterocyclic Compounds, pubmed-meshheading:21056990-Lung Neoplasms, pubmed-meshheading:21056990-Lymphatic Metastasis, pubmed-meshheading:21056990-Lymphatic Vessels, pubmed-meshheading:21056990-Melanoma, Experimental, pubmed-meshheading:21056990-Mice, pubmed-meshheading:21056990-Mice, Inbred C57BL, pubmed-meshheading:21056990-Mice, Transgenic, pubmed-meshheading:21056990-Peptides, pubmed-meshheading:21056990-Receptors, CXCR4, pubmed-meshheading:21056990-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche.
pubmed:affiliation
National Research Laboratory of Vascular Biology and Stem Cells, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't