title: Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent.
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.
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA. ihare@mix.wvu.edu.|Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9104, Morgantown, WV, USA. ihare@mix.wvu.edu.
authors: Ian
authors: http://orcid.org/0000-0003-4744-3231
authors: I
authors: Hare
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.
authors: Rebecca
authors: R
authors: Evans
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.
authors: James
authors: J
authors: Fortney
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.
authors: Blake
authors: B
authors: Moses
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.
authors: Debbie
authors: D
authors: Piktel
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.
authors: William
authors: W
authors: Slone
authors: Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9300, Morgantown, WV, USA.|Department of Microbiology, Immunology, and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, PO Box 9104, Morgantown, WV, USA.
authors: Laura F
authors: LF
authors: Gibson
mesh_terms: D002478:Cells, Cultured; D005047:Etoposide / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008558:Melphalan / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D008558:Melphalan
keywords: Chemotherapy; Dkk-1; Mesenchymal Stem Cell; Tumor Microenvironment; Wnt Signaling