The role of hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 in endometrial cancer.
Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and HAI-2 in endometrial cancer. We investigated the biological functions of HAI-1 and HAI-2 using KLE and HEC-251 endometrial cancer cell lines, thus HAI-1 and HAI-2 were examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. HAI-1 and HAI-2 showed potential inhibitory effects on cell proliferation, migration and cellular invasion by reduction of matriptase and hepsin expression. This in turn led to an increase in the levels of E-cadherin and Slug, and a reduction in the levels of Vimentin, SIP1, Snail and Twist, and hence ER and PR signal transduction in endometrial cancer cells. The levels of HAI-1 and HAI-2 expression were significantly decreased in endometrial cancer specimens relative to the corresponding normal endometrium specimens. Low HAI-1 and HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-1 and HAI-2 expression. These findings indicate that HAI-1 and HAI-2 could be considered as therapeutic targets and used as favorable prognosis markers for endometrial cancer.
Nakamura
Keiichiro
K
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. k-nakamu@cc.okayama-u.ac.jp
Hongo
Atsushi
A
Kodama
Junichi
J
Hiramatsu
Yuji
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C109149:SPINT1 protein, human; C109148:SPINT2 protein, human