Wnt Signaling in Prostate Cancer Bone Metastases
Abstract
Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced Wnt/JNK signaling could alter tumor growth, metastasis and the bone microenvironment. Evidence was found that Dkk-1 up-regulated the non-canonical Wnt/JNK pathway resulting with downstream alterations in gene expression important for osteoblast stimulation, cell proliferation and epithelial-to-mesenchymal transformation of cancer cells. Inhibition of non-canonical Wnt/JNK signaling using SP600125 (JNK inhibitor)significantly increased the mRNA expression of genes that induced bone formation as well as decreased osteoclastic bone lysis in vitro. Dkk-1 increased tumor volume in mice. When mice were injected subcutaneously with Ace-1-Dkk1, treatment with SP600125 significantly reduced tumor size and altered tumor cell morphology. However, treatment with SP600125 did not alter tumor size in mice that were injected intra-tibially with Ace-1-Dkk1. Inhibition of non-canonical Wnt/JNK signaling using SP600125 resulted in decreased tumor volume but did not alter tumor size in the bone.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2016
- Accession Number
- AD1031106
Entities
People
- Wachiraphan Supsavhad
Organizations
- Ohio State University