title: Keratinocyte growth factor induces matrix metalloproteinase-9 expression             and correlates with venous invasion in pancreatic cancer.
abstract: Keratinocyte growth factor (KGF), also known as fibroblast growth factor-7,             and KGF receptor (KGFR) play important roles in the growth of epithelial cells             and are overexpressed in a variety of malignant epithelial tumors, including pancreatic             ductal adenocarcinoma (PDAC). We previously reported that co-expression of KGF             and KGFR in PDAC is associated with venous invasion, enhanced vascular endothelial             growth factor A expression and poor prognosis. Matrix metalloproteinase-9 (MMP-9)             is known to participate in the degradation of type IV collagen, which is a primary             component of extracellular matrices in the vascular basement membrane. In the             present study, we examined the expression and roles of KGF, KGFR and MMP-9 in             human PDAC cell lines and tissues. Quantitative real-time polymerase chain reaction             analysis demonstrated the expression of MMP-9 mRNA in all eight PDAC cell lines.             KGF, KGFR and MMP-9 were, respectively, expressed in 27 (43%), 23 (37%) and 35             (56%) of 63 patients. Each expression of KGF, KGFR or MMP-9 correlated positively             with venous invasion. Furthermore, expression of KGF or MMP-9 correlated positively             with liver metastasis. KGF-positive cases exhibited shorter survival than KGF-negative             cases, while KGFR and MMP-9 expression were unrelated to prognosis. Administration             of recombinant human KGF increased MMP-9 expression in PDAC cells, while transient             transfection with short hairpin RNAs targeting KGF transcripts reduced MMP-9 expression             in PDAC cells. Moreover, recombinant human KGF significantly enhanced migration             and invasion of PDAC cells. These findings suggest that KGF and KGFR promote venous             invasion via MMP-9 in PDAC, and closely correlate with liver metastasis. The KGF/KGFR             pathway may be a critical therapeutic target for PDAC metastasis.
authors.affiliation: Departments of Pathology and Integrative Oncological Pathology,                     Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Cho
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Junji
authors.initials: J
authors.lastname: Ueda
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051523:Fibroblast Growth Factor 7; D020780:Matrix Metalloproteinase 9