Document Detail


Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells.
MedLine Citation:
PMID:  23775727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many targets have been identified in solid tumors for antibody therapy but it is less clear what surface antigens may be most commonly expressed on disseminated tumor cells. Using malignant pleural effusions as a source of disseminated tumor cells, we compared a panel of 35 antigens for their cancer specificity, antigen abundance and functional significance. These antigens have been previously implicated in cancer metastasis and fall into four categories: (i) cancer stem cell, (ii) epithelial-mesenchymal transition, (iii) metastatic signature of in vivo selection and (iv) tyrosine kinase receptors. We determined the antigen density of all 35 antigens on the cell surface by flow cytometry, which ranges from 3 × 10(3) -7 × 10(6) copies per cell. Comparison between the malignant and benign pleural effusions enabled us to determine the antigens specific for cancer. We further chose six antigens and examined the correlation between their expression levels and tumor formation in immunocompromised mice. We concluded that CD24 is one of the few antigens that could simultaneously meet all three criteria of an ideal target. It was specifically and abundantly expressed in malignant pleural effusions; CD24(high) tumor cells formed tumors in mice at a faster rate than CD24(low) tumor cells, and shRNA-mediated knockdown of CD24 in HT29 cells confirmed a functional requirement for CD24 in the colonization of the lung. Concomitant consideration of antigen abundance, specificity and functional importance can help identify potentially useful markers for disseminated tumor cells.
Authors:
Xiaosai Yao; Myriam Labelle; Carla R Lamb; John M Dugan; Christina A Williamson; Donna R Spencer; Kimberly R Christ; Ryan O Keating; W David Lee; Glenn A Paradis; Shahinoor Begum; Richard O Hynes; K Dane Wittrup
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Publication Detail:
Type:  Journal Article     Date:  2013-07-13
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-10-14     Completed Date:  2013-12-09     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2925-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD24 / analysis*,  physiology
Antigens, Neoplasm / analysis
Antigens, Surface / analysis*
Cell Adhesion Molecules / analysis
HT29 Cells
Heterografts
Humans
Lung Neoplasms / secondary
Mice
Neoplasm Transplantation
Pleural Effusion, Malignant / immunology*,  pathology
Tumor Markers, Biological / analysis*
Grant Support
ID/Acronym/Agency:
P30 CA014051/CA/NCI NIH HHS; R01 CA096504/CA/NCI NIH HHS; R01 CA101830/CA/NCI NIH HHS; R01 CA174795/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD24; 0/Antigens, Neoplasm; 0/Antigens, Surface; 0/CD24 protein, human; 0/Cell Adhesion Molecules; 0/Tumor Markers, Biological; 0/tumor-associated antigen GA733

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