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Chemotherapy-induced Dkk-1 Expression by Primary Human Mesenchymal Stem Cells Is p53 Dependent

Chemotherapy-induced Dkk-1 Expression by Primary Human Mesenchymal Stem Cells Is p53 Dependent

Ian Hare, Rebecca Evans, James Fortney, Blake Moses, Debbie Piktel, William Slone, Laura F Gibson

Med Oncol. 2016 Oct;33(10):113.

PMID: 27586146

Abstract:

Mesenchymal stem cells (MSCs) are abundant throughout the body and regulate signaling within tumor microenvironments. Wnt signaling is an extrinsically regulated pathway that has been shown to regulate tumorigenesis in many types of cancer. After evaluating a panel of Wnt activating and inhibiting molecules, we show that primary human MSCs increase the expression of Dkk-1, an inhibitor of Wnt signaling, into the extracellular environment following chemotherapy exposure in a p53-dependent manner. Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4246413	DKK-1 human			Price

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