Expression of CD176 (Thomsen-Friedenreich antigen) on lung, breast and liver cancer-initiating cells.
The cancer-initiating capacity of most malignant tumours is considered to reside in a small subpopulation of cells. Therapeutical interventions should target these cells rather than the tumour mass. Numerous studies have shown that the carbohydrate antigen structure CD176 (Thomsen-Friedenreich antigen, core-1) is present in many types of cancer and absent in normal adult human tissues. In this study, we assessed whether CD176 is co-expressed with CD44 or CD133 [markers of cancer-initiating cells (CIC)] in human lung, breast and liver carcinoma. A variety of human cancer cell lines and surgical specimens of these malignancies were examined. It was found that in most cases the majority of tumour cells stained strongly for CD44 by immunohistochemistry and flow cytometry, whereas CD133 expression was found on a smaller, but varying proportion of cells. Co-expression of CD176 with CD44 was found at a surprisingly high percentage of cancer cells in vitro and in vivo. Co-expression of CD176 with CD133 was also detected, although at a lower rate. Tamoxifen treatment of MDA-435 breast cancer cells enhanced the CD44(+) /CD176(+) phenotype. Evidence is provided through a new sandwich solid-phase enzyme-linked immunosorbent assay (ELISA) suggesting that CD44 is a carrier molecule for CD176 not only in colorectal cancer as previously reported, but also in lung, breast and liver cancer. The expression of CD176 in CIC suggests that it may represent an effective target for tumour therapies.
Key Laboratory of Animal Models and Human Disease Mechanisms of CAS and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Wei-Ming
WM
Lin
Uwe
U
Karsten
Steffen
S
Goletz
Ruo-Chuan
RC
Cheng
Yi
Y
Cao
D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D007519:Isoantigens; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D011956:Receptors, Cell Surface; D013629:Tamoxifen / Q000494:pharmacology
D000071916:AC133 Antigen; D015703:Antigens, CD; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D007519:Isoantigens; C000606023:PROM1 protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D013629:Tamoxifen; C016467:Thomsen-Friedenreich antigen