title: Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential.
abstract: OBJECTIVE
  Migrating cancer stem cells (MCSCs) are believed to form metastases. We sought to identify markers of MCSCs from human colorectal cancers (CRCs) and determine their roles in organ-specific metastasis.
  
  
  METHODS
  To identify colorectal MCSCs that contribute to organ-specific metastasis, we developed a model of liver or lung metastasis using primary tumor cells from patients with CRC who had liver and lung metastases. Distinct organ-specific metastatic cells were isolated by 6 cycles of selecting for cells that formed liver and lung tumors after subcutaneous injection into mice. Microarray analysis was used to identify markers of the organ-specific MCSCs. We then measured levels of these markers in CRC cell lines and 128 CRC samples. We characterized the functional roles of these markers in organ-specific metastasis.
  
  
  RESULTS
  We identified CD110 and CDCP1 as cell surface markers of MCSCs from human colorectal tumors that metastasized to liver and lung. We observed a distinct pattern of CD110 and CDCP1 in a panel of primary colorectal tumor samples and their matched liver or pulmonary metastases, indicating that these proteins might serve as biomarkers of organ-specific metastasis. Functional studies showed that thrombopoietin attracts CD110(+) CSCs and increases their self-renewal to promote formation of liver metastases. CDCP1 promoted adhesion of CRC cells to the lung endothelium.
  
  
  CONCLUSIONS
  We isolated MCSCs from primary human CRCs and found that the CD110(+) and CDCP1(+) subpopulations mediate organ-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.
authors.affiliation: Department of General Surgery, Second Military Medical University, Shanghai, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Gao
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ma
authors.forename: Zunguo
authors.initials: Z
authors.lastname: Du
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Hu
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000556:secondary*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D053628:Receptors, Thrombopoietin / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human
keywords: 5-FU; 5-fluoropyrimidine; CRC; CRLM; CRPM; CSC; Colon Cancer; GFP; Initiation; MCSC; PCR; Prognosis; TPO; Tumor Progression; cancer stem cell; colorectal cancer; colorectal liver metastases; colorectal pulmonary metastases; green fluorescent protein; migrating cancer stem cell; polymerase chain reaction; thrombopoietin