title: Activation of pro-gelatinase B by endometase/matrilysin-2 promotes invasion of human prostate cancer cells.
abstract: This work has explored a putative biochemical mechanism by which endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) may promote human prostate cancer cell invasion. Here, we showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. The role of MMP-26 in prostate cancer progression is unknown. MMP-26 was capable of activating pro-MMP-9 by cleavage at the Ala(93)-Met(94) site of the prepro-enzyme. This activation proceeded in a time- and dose-dependent manner, facilitating the efficient cleavage of fibronectin by MMP-9. The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested. To investigate the contribution of MMP-26 to cancer cell invasion via the activation of MMP-9, highly invasive and metastatic human prostate carcinoma cells, androgen-repressed prostate cancer (ARCaP) cells were selected as a working model. ARCaP cells express both MMP-26 and MMP-9. Specific anti-MMP-26 and anti-MMP-9 functional blocking antibodies both reduced the invasiveness of ARCaP cells across fibronectin or type IV collagen. Furthermore, the introduction of MMP-26 antisense cDNA into ARCaP cells significantly reduced the MMP-26 protein level in these cells and strongly suppressed the invasiveness of ARCaP cells. Double immunofluorescence staining and confocal laser scanning microscopic images revealed that MMP-26 and MMP-9 were co-localized in parental and MMP-26 sense-transfected ARCaP cells. Moreover, MMP-26 and MMP-9 proteins were both expressed in the same human prostate carcinoma tissue samples examined. These results indicate that MMP-26 may be a physiological and pathological activator of pro-MMP-9.
authors.affiliation: Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4390, USA.
authors.forename: Yun-Ge
authors.initials: YG
authors.lastname: Zhao
authors.forename: Ai-Zhen
authors.initials: AZ
authors.lastname: Xiao
authors.forename: Robert G
authors.initials: RG
authors.lastname: Newcomer
authors.forename: Hyun I
authors.initials: HI
authors.lastname: Park
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.forename: Mark G
authors.initials: MG
authors.lastname: Swanson
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.forename: Qing-Xiang Amy
authors.initials: QX
authors.lastname: Sang
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D024141:Collagen Type IV; D004792:Enzyme Precursors; D005353:Fibronectins; D020319:Oligodeoxyribonucleotides, Antisense; D018093:Gelatinases; C410599:MMP26 protein, human; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C069860:progelatinase