The
hepatocyte growth factor (HGF) pathway has been well documented as playing a vital role in the progression and development of many different types of human
cancers; as such this pathway is usually tightly regulated. In
cancer cells, the regulation of this pathway has been shown to be disrupted, allowing an increase in activation of
pro-HGF to active HGF. There are a number of molecules capable of activating
pro-HGF, such as matriptase-1, a type II transmembrane
serine protease, or
hepatocyte growth factor activator, and in turn, these are also subject to regulation. In the current study we examined the importance of
hepatocyte growth factor activator inhibitor-1 (HAI-1) which is known to inhibit a number of HGF-activating molecules. We reduced the expression of this molecule in both PC-3 and DU-145 cell lines using
hammerhead ribozyme technology, and we examined various important characteristics associated with
cancer progression and development in vitro.
Prostate cancer cells, after loss of HAI-1, had a significantly increased in vitro invasiveness together with an increase in cellular motility. Notably, loss of HAI-1 resulted in a slower rate of cell growth over a prolonged period (5 days). This in vitro evidence collectively suggests that the suppression of HAI-1 expression gives rise to a more aggressive
cancer cell phenotype. This implies that
therapies inducing the overexpression of HAI-1 or delivering an exogenous source of HAI-1
protein may hold potential as a treatment to slow the progression of
prostate cancer.