Medical Oncology

, 33:113 | Cite as

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
Short Communication


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.


Chemotherapy Wnt Signaling Tumor Microenvironment Dkk-1 Mesenchymal Stem Cell 



This work was funded by National Institutes of Health (NIH) R01 HL056888 (LFG), NIH P20 RR016440 (LFG), National Cancer Institute (NCI) RO1 CA134573 (LFG), WV CTR-IDEA NIH 1U54 GM104942, CoBRE P30GM103488, The Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program, and The WV Research Trust Fund. The authors would like to thank Dr. James Coad for providing de-identified bone marrow specimens.

Compliance with ethical standards

Conflict of interest


Supplementary material

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Supplemental Figure 3 (EPS 1628 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences CenterWest Virginia University School of MedicineMorgantownUSA
  2. 2.Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences CenterWest Virginia University School of MedicineMorgantownUSA

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