Paracrine sonic hedgehog signalling by prostate cancer cells induces osteoblast differentiation

Abstract

Background: Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Noncanonical Regulation of the Hedgehog Mediator GLI1 by c-MYC in Burkitt Lymphoma

“…We detected changes in GLI1 expression only in BL2625 cells exposed to SHH, which are of questionable biologic significance. We show increased GLI1 and PTCH1 expression in MC3T3 mouse preosteoblast, which have been previously shown to be Hedgehog-responsive cells (15). In addition, we do not detect significant changes in cell viability measured by MTT assays, cell proliferation measured by BrdUrd assays, or apoptosis measured by caspase-3/7 assays Figure 2.…”

“…15), or to IHH peptide (R&D Systems). The cells were incubated for 24 hours at 37 C with serum-free culture media containing 1 mg/mL Hedgehog peptide.…”

Prostate Cancer Cells and Bone Stromal Cells Mutually Interact with Each Other through Bone Morphogenetic Protein-mediated Signals

“…Prostate cancer cells produce endothelin-1, urokinase-type plasminogen activator, and prostate-specific antigen, and these stimulate the biological activity of osteoblasts (28). In addition, SHH, which is produced by prostate cancer cells, is known to promote the differentiation of osteoblasts (29). Here, we showed the important role of BMPs and BMP-induced SHH as inducers of the osteoblastic differentiation of bone stromal cells (Fig.…”

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

“…Although Hedgehog signaling (mediated by either Indian or Sonic) has been observed to enhance the osteogenic differentiation in numerous bone forming cells in vitro (Ho et al, 2007;James et al, 2010;Jemtland et al, 2003;Levi et al, 2011;Nakamura et al, 1997;Spinella-Jaegle et al, 2001;Yuasa et al, 2002;van der Horst et al, 2003;Wu et al, 2004;Zunich et al, 2009), the precise effects of Ihh in calvarial ossification have not been yet defined. Toward this end, Abzhanov et al studied Ihh misexpression in chick and mouse calvaria.…”