Increased in situ gelatinolytic activity in renal cell tumor tissues correlates with tumor size, grade and vessel invasion.
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.
Kamiya
Naoto
N
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kishimoto
Takashi
T
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Suzuki
Hiroyoshi
H
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Sekita
Nobuyuki
N
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nagai
Yuichiro
Y
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Oosumi
Nobuyuki
N
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kito
Hiroki
H
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Tochigi
Naobumi
N
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shinbo
Masataka
M
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nemori
Ryouichi
R
Ashigara Research Laboratories, Fuji Photo Film Co. Ltd., Japan.
Ichikawa
Tomohiko
T
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Igarashi
Tatsuo
T
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ito
Haruo
H
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ishikura
Hiroshi
H
Department of Molecular Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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
C015233:gelatin film; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9