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Matrix Metalloproteinases-2 and 9 Do Not Play a Role in the Growth of Preneoplastic Liver Lesions in F344 Rats
- Source :
- Experimental Biology and Medicine. 226:799-803
- Publication Year :
- 2001
- Publisher :
- SAGE Publications, 2001.
-
Abstract
- Matrix metalloproteinases- (MMPs) 2 and 9 (gelatinases A and B) have been implicated in tumor invasion and metastasis, and recent studies have shown increased levels of these enzymes during recovery from partial hepatectomy (PH) in rats. F344 rats are highly susceptible to the growth of glutathione S-transferase 7-7- (GST 7-7) positive preneoplastic liver lesions promoted using the modified resistant hepatocyte (RH) protocol. Since the RH protocol consists of 2-acetylaminofluorene (2-AAF) followed by a PH, we reasoned that MMP-2 and -9 might be critical for the growth of lesions. Using gelatin zymography, we examined the expression of these enzymes in the livers of F344 rats treated with the RH protocol and sacrificed on Days 2, 4, 7, 14, and 21 after 2-AAF/PH. We found increases in both pro- and active MMP-2 and -9 over baseline levels, with the highest levels occurring on Day 7 post-PH. Also, a 54-kDa band, likely to be proMMP-1, was elevated in a pattern similar to MMP-2 and -9. In contrast to F344 rats, identically treated Copenhagen rats that are highly resistant to promotion of liver lesion growth using the RH protocol had significantly lower levels of proMMP-1 and -2. To test the importance of these MMPs to the growth of liver lesions, F344 rats that had been initiated with diethylnitrosamine were treated using the RH protocol. They then received either the MMP inhibitor batimastat (30 mg/kg, intraperitoneally) or vehicle alone daily from Day 3 to 20 post-PH and were sacrificed on Day 21. There were no differences in the percentage of liver volume occupied by GST 7-7-positive lesions (19.1 ± 4.84 vs 19.4 ± 3.31, treated versus vehicle, mean ± SEM) or liver weight as a percentage of body weight (4.11% ± 0.15 vs 4.07% ± 0.18, treated versus vehicle, mean ± SEM) between the treated and control groups. Treatment of rats with batimastat clearly did not affect lesion growth or liver regeneration following the RH protocol. These results suggest that increases in gelatinase expression during the RH protocol are a result of the promotional stimulus rather than a mechanism by which 2-AAF/PH causes lesion growth.
- Subjects :
- 0301 basic medicine
Alkylating Agents
medicine.medical_specialty
Pathology
Time Factors
Matrix metalloproteinase
General Biochemistry, Genetics and Molecular Biology
Metastasis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Gelatinase
Diethylnitrosamine
Glutathione Transferase
chemistry.chemical_classification
Chemistry
Liver Neoplasms
Glutathione
medicine.disease
Rats, Inbred F344
Liver regeneration
Rats
030104 developmental biology
Endocrinology
Enzyme
medicine.anatomical_structure
Liver
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Hepatocyte
Matrix Metalloproteinase 2
Precancerous Conditions
Batimastat
Densitometry
Subjects
Details
- ISSN :
- 15353699 and 15353702
- Volume :
- 226
- Database :
- OpenAIRE
- Journal :
- Experimental Biology and Medicine
- Accession number :
- edsair.doi.dedup.....e173ea1b99fd99748646d99848f64bd9