Original ResearchBasic and Translational-Alimentary TractMesenchymal Stem Cells Promote Formation of Colorectal Tumors in Mice
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Primary Cells and Cell Lines
The human colorectal cancer cell line HT-29 was obtained from the American Type Culture Collection and grown in Dulbecco's modified Eagle medium (Gibco, Grand Island, NY) containing 100 U/mL penicillin, 100 μg/mL streptomycin, 4 mmol/L glutamine, and 10% fetal bovine serum (Gibco). The MSC cell line was immortalized by retroviral transduction of HPV16 E6E7 and grown in Dulbecco's modified Eagle medium–low glucose (Gibco) supplemented with 10% fetal bovine serum.8 Primary MSCs from different
Nontransformed Cells Derived From Various Tissues Promote Colorectal Tumor Initiation and Tumor Sphere Formation
To investigate the functional consequences of the heterotypic interactions between HT-29 colorectal cancer cells (CCCs) and nontransformed cells (NTCs) derived from various tissues, the growth kinetics of the nontransformed cells containing tumors (CCCs plus NTCs) was compared with those of CCCs or NTCs alone in a xenograft model of immunocompromised mice. We found that co-injection with MSCs, WI38 lung fibroblasts, primary DFs, or primary GE, but not with 293 adenoviral-transfected human
Discussion
Recently, tumors formed by an unsorted single tumor cell after transplantation into a highly immunocompromised mouse (with IL-2–receptor-γ chain deletion in nonobese diabetic/severe combined immunodeficient mice) was achieved in melanoma.23 The current study also showed a single unsorted or CD133-CD166-EpCAM triple-negative colorectal cancer cell admixed with MSCs, up to 5%–7% of the injections formed tumors in mice. It is yet to be determined whether the MSC-enhanced TICs in colon cancer also
Acknowledgments
S.-H.Y. and Y.-P.L. contributed equally to this article.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the National Science Council (3111-B-039, 96-2627-B-010-009, 97-3111-B-010-001, and 99-3111-B-010-005-), Taipei Veterans General Hospital (V97C1-060, V98C1-009, and V98E1-002), the MD Anderson Cancer Center/China Medical University and Hospital Sister Institution Fund, and the National Yang-Ming University, Ministry of Education. This work was assisted in part by the Division of Experimental Surgery of the Department of Surgery, Taipei Veterans General Hospital.