Document Detail


CD147-dependent heterogeneity in malignant and chemoresistant properties of cancer cells.
MedLine Citation:
PMID:  23178078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD147 (alias emmprin or basigin), an integral plasma membrane glycoprotein and a member of the Ig superfamily, is widespread in normal tissues, but highly up-regulated in many types of malignant cancer cells. CD147 is multifunctional, with numerous binding partners. Recent studies suggest that complexes of CD147 with the hyaluronan receptor CD44 and associated transporters and receptor tyrosine kinases are enriched in the plasma membrane of cancer stem-like cells. Here, we show that subpopulations of tumor cell lines constitutively expressing high levels of cell-surface CD147 exhibit cancer stem-like cell properties; that is, they exhibit much greater invasiveness, anchorage-independent growth, spheroid formation, and drug resistance in vitro and higher tumorigenicity in vivo than those constitutively expressing low levels of cell-surface CD147. Primary CD147-rich cell subpopulations derived from mouse mammary adenocarcinomas also exhibit high levels of invasiveness and spheroid-forming capacity, whereas CD147-low cells do not. Moreover, localization at the plasma membrane of CD44, the EGF receptor, the ABCB1 and ABCG2 drug transporters, and the MCT4 monocarboxylate transporter is elevated in cells constitutively expressing high levels of cell-surface CD147. These results show that CD147 is associated with assembly of numerous pro-oncogenic proteins in the plasma membrane and may play a fundamental role in properties characteristic of cancer stem-like cells.
Authors:
Lu Dai; Maria C Guinea; Mark G Slomiany; Momka Bratoeva; G Daniel Grass; Lauren B Tolliver; Bernard L Maria; Bryan P Toole
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-22
Journal Detail:
Title:  The American journal of pathology     Volume:  182     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-07-09     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  577-85     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD147 / metabolism*
Antigens, CD44 / metabolism
Cell Adhesion
Cell Line, Tumor
Cell Membrane / metabolism
Cell Proliferation
Cell Transformation, Neoplastic / pathology
Drug Resistance, Neoplasm*
Female
Flow Cytometry
Genetic Heterogeneity*
Humans
Mammary Neoplasms, Animal
Mammary Tumor Virus, Mouse
Mice
Neoplasm Invasiveness
Neoplasms / metabolism*,  pathology*
Receptor, Epidermal Growth Factor / metabolism
Spheroids, Cellular / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
C06-RR015455/RR/NCRR NIH HHS; P30-CA138313/CA/NCI NIH HHS; R01-CA073839/CA/NCI NIH HHS; R01-CA082867/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD44; 136894-56-9/Antigens, CD147; EC 2.7.10.1/Receptor, Epidermal Growth Factor
Comments/Corrections

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