Hepatocyte growth factor activation inhibitors - therapeutic potential in cancer.
Hepatocyte growth factor (HGF) plays a plethora of roles in the progression of many invasive and metastatic cancers. The interaction between tumour cells and their surrounding stromal environment remains a crucial factor governing tumour invasion and metastasis. HGF is primarily synthesised by stromal fibroblasts as an inactive precursor known as pro-HGF. A number of proteases have demonstrated the ability to convert pro-HGF into the biologically active form of HGF, although the two main factors responsible are HGF activator (HGFA) and matriptase. The HGF activation inhibitors (HAI-1 and HAI-2) are two novel Kunitz-type serine protease inhibitors that regulate HGFA and matriptase activity to govern the influence of HGF within the body. Deregulation of HAI expression can lead to shift in the HGF activation/inhibition balance ratio in favour of enhanced HGF production. Therefore, these HGF activation inhibitors may have a direct bearing on cancer invasion and metastasis. This review examines the accumulating evidence on the emerging role and therapeutic potential of HAI-1 and HAI-2 in cancer.
Parr
Christian
C
Cardiff University, UK. parrc@cf.ac.uk
Sanders
Andrew J
AJ
Jiang
Wen G
WG
D045744:Cell Line, Tumor; D017228:Hepatocyte Growth Factor / Q000819:agonists / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D015842:Serine Proteinase Inhibitors; D017228:Hepatocyte Growth Factor