Figure 9. Summary diagram shows how recombinant PN1 added in Matrigel (a) can influence Hh proteins in both autocrine and paracrine scenarios.

PN1 disrupts reduces SHH expression, leading to reduction of downstream Hh effectors and tumor growth. Treatment with Hh inhibitor (b) GDC-0449 blocks another avenue of Hh signaling leading to inhibition of SMO. The combined effect slows the growth of prostate metastatic cells, potentially through changes in angiogenesis. The PN1 arm of the pathway can be inhibited by MMP9 activity.