期刊
CELL CYCLE
卷 10, 期 14, 页码 2331-2338出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.10.14.16418
关键词
IGF-1; cancer stem cell; colon cancer; figitumumab
类别
资金
- NIH [CA135273, CA094214]
- Littlefield-AACR
- [T32 DK00780]
Cancer stem cells (CSCs) are recognized as contributors of cancer progression and therapeutic resistance in liquid and solid malignancies. We analyzed a panel of human colon cancer cell lines for CSC populations by side population and aldehyde dehydrogenase activity. IGF-1 enriches these putative colon CSC populations in a beta-catenin-dependent manner. Chemical inhibition of Akt depletes SP cells, and conversely, the overexpression of a constitutively active mutant version of Akt is sufficient to enrich CSC populations. CP-751,871, a fully human antibody with specificity to the IGF-1 receptor, is currently being tested in clinical trials for a variety of solid tumors. CP-751,871 reduces CSC populations in colon cancer cell lines in vitro and reduces tumor growth in vivo. We have identified a novel role for IGF-1 in the enrichment of chemo-resistant CSC populations. Our results suggest that CP-751,871 has preferential activity against putative CSC populations and therefore, may compliment current standard chemotherapeutic regimens that target cycling cells.
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