Human colon cancer stem cells are enriched by insulin-like growth factor-1 and are sensitive to figitumumab

被引：60

作者：

Hart, Lori S. ^{[2
]}

Dolloff, Nathan G. ^{[1
]}

Dicker, David T. ^{[1
]}

Koumenis, Constantinos ^{[2
]}

Christensen, James G. ^{[4
]}

Grimberg, Adda ^{[3
]}

El-Deiry, Wafik S. ^{[1
]}

机构：

[1] Penn State Hershey Canc Inst, Hershey Med Ctr, Dept Med, Div Hematol Oncol, Hershey, PA USA

[2] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Dept Endocrinol, Philadelphia, PA 19104 USA

[4] Pfizer Global R&D, Translat Pharmacol, La Jolla, CA USA

来源：

CELL CYCLE | 2011年 / 10卷 / 14期

关键词：

IGF-1; cancer stem cell; colon cancer; figitumumab; HUMAN COLORECTAL-CANCER; ACUTE MYELOID-LEUKEMIA; DRUG EFFLUX CAPACITY; SIDE-POPULATION; CD133; EXPRESSION; BREAST-CANCER; RECEPTOR; MARKER; IDENTIFICATION; METASTASIS;

D O I：

10.4161/cc.10.14.16418

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2331 / 2338

页数：8

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