title: Increased in situ gelatinolytic activity in renal cell tumor tissues correlates with tumor size, grade and vessel invasion.
abstract: Degradation of collagen, or gelatinolysis, by tumor cells is one of the most important events in tumorigenesis. We investigate the possible relationship between the in situ gelatinolytic activities exerted by matrix metalloproteinases (MMPs) and clinico-pathological factors in renal cell tumor (RCT) patients. Using the film in situ zymography (FIZ) method, we determined in situ localization of MMP-like gelatinolytic activities in cancerous and normal tissues in the kidney (n = 51). To clarify the MMP(s) responsible for the gelatinolytic activity in RCTs, we examined the expressions of MMP-2 and MMP-9 in the kidney tissues by means of gelatin zymography (GZG). MMP expression was also detected by RT-PCR and Western blotting analysis. We then investigated the associations of MMP expression, as detected by GZG, with the intensity of gelatinolytic activity, as determined by FIZ. We analyzed the possible relationship of FIZ findings to several clinico-pathological factors such as tumor size, grade, vessel invasion, histologic type, stage and metastasis. FIZ demonstrated that all tumor and normal kidney tissues showed in situ gelatinase activities, and that gelatinolytic activities in RCTs were much stronger than those of normal kidney tissues. There was a statistically significant correlation between the intensity of MMP-like gelatinolytic activity and tumor size, tumor grade and vessel invasion (p < 0.05), but not between it and histological type, tumor stage or metastatic status. FIZ showed that tumor tissues in 5 of the 6 patients with fatal outcome exhibited the intense gelatinolytic pattern. Stronger in situ gelatinolytic patterns were documented in cases with higher MMP-2 expression. The molecular species of MMPs detected by GZG were confirmed by RT-PCR and Western blotting analysis. The FIZ technique enables a direct assessment of in situ gelatinolytic activity in RCT tissues. The intensity of the activity seems to affect the biology of RCT tissues. Our results also indicate a major role for MMP-2 in in situ gelatinolysis in RCT tissues.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kamiya
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sekita
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oosumi
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kito
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naobumi
authors.initials: N
authors.lastname: Tochigi
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Shinbo
authors.affiliation: Ashigara Research Laboratories, Fuji Photo Film Co. Ltd., Japan.
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Nemori
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D018262:Adenocarcinoma, Clear Cell / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C015233:gelatin film; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9