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Abstract Title:

Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction.

Abstract Source:

Stem Cells. 2008 Jul ;26(7):1818-30. Epub 2008 May 8. PMID: 18467664

Abstract Author(s):

Bikul Das, Rika Tsuchida, David Malkin, Gideon Koren, Sylvain Baruchel, Herman Yeger

Article Affiliation:

Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

Abstract:

Although advances have been made in understanding the role of hypoxia in the stem cell niche, almost nothing is known about a potentially similar role of hypoxia in maintaining the tumor stem cell (TSC) niche. Here we show that a highly tumorigenic fraction of side population (SP) cells is localized in the hypoxic zones of solid tumors in vivo. We first identified a highly migratory, invasive, and tumorigenic fraction of post-hypoxic side population cells (SPm([hox]) fraction) in a diverse group of solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, and small-cell lung carcinoma. To identify the SPm((hox)) fraction, we used an"injured conditioned medium"derived from bone marrow stromal cells treated with hypoxia and oxidative stress. We found that a highly tumorigenic SP fraction migrates to the injured conditioned medium in a Boyden chamber. We show that as few as 100 SPm((hox)) cells form rapidly growing tumors in vivo. In vitro exposure to hypoxia increases the SPm((hox)) fraction significantly. Quantitative real-time polymerase chain reaction and immunofluorescence studies showed that SPm((hox)) cells expressed Oct-4, a"stemness"gene having a potential role in TSC maintenance. In nude mice xenografts, SPm((hox)) cells were localized to the hypoxic zones, as demonstrated after quantum dot labeling. These results suggest that a highly tumorigenic SP fraction migrates to the area of hypoxia; this migration is similar to the migration of normal bone marrow SP fraction to the area of injury/hypoxia. Furthermore, the hypoxic microenvironment may serve as a niche for the highly tumorigenic fraction of SP cells.

Study Type : Review
Additional Links
Anti Therapeutic Actions : Hypoxia : CK(22) : AC(4)
Adverse Pharmacological Actions : Cancer Stemness Inducer : CK(4) : AC(4)

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Sayer Ji
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