title: Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells.
abstract: 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.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Xiaosai
authors.initials: X
authors.lastname: Yao
authors.forename: Myriam
authors.initials: M
authors.lastname: Labelle
authors.forename: Carla R
authors.initials: CR
authors.lastname: Lamb
authors.forename: John M
authors.initials: JM
authors.lastname: Dugan
authors.forename: Christina A
authors.initials: CA
authors.lastname: Williamson
authors.forename: Donna R
authors.initials: DR
authors.lastname: Spencer
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Christ
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Keating
authors.forename: W David
authors.initials: WD
authors.lastname: Lee
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Paradis
authors.forename: Shahinoor
authors.initials: S
authors.lastname: Begum
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
authors.forename: K Dane
authors.initials: KD
authors.lastname: Wittrup
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D051927:CD24 Antigen / Q000032:analysis* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis; D000071858:Epithelial Cell Adhesion Molecule; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009368:Neoplasm Transplantation; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule
keywords: CD24; disseminated tumor cells; flow cytometry; pleural effusions; surface biomarker