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Gastroenterology. 2013 Sep;145(3):636-46.e5. doi: 10.1053/j.gastro.2013.05.049. Epub 2013 Jun 5.

Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential.

Author information

  • 1Department of General Surgery, Second Military Medical University, Shanghai, China.

Abstract

BACKGROUND & AIMS:

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.

Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

PMID:
23747337
[PubMed - indexed for MEDLINE]
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