Deregulation of collagen metabolism in human stomach cancer.
OBJECTIVE
The defects of collagen metabolism are responsible for the disorganization of extracellular matrix in stomach cancer. Collagen through interaction with integrin receptors regulates the cellular growth, differentiation, gene expression, prolidase and gelatinase activity and plays an important role in tumorigenesis and invasiveness. Although extracellular metalloproteinases initiate the breakdown of collagen in tissues, the final step of its degradation is mediated by prolidase. Therefore, we decided to compare the degradation of collagen in control tissues to gastric cancer tissues.


METHODS
We investigated the collagen content (hydroxyproline assay), expressions of beta(1) integrin, prolidase and gelatinases A and B (Western immunoblot) as well activities of prolidase (colorimetric assay) and gelatinases (zymography) in stomach cancer tissue (n = 10). The results were compared with corresponding data obtained for control tissues (n = 10).


RESULTS
No differences in the collagen content were found between the studied tissue samples. However, an increase in free proline pool, enhanced gelatinase expression and elevated gelatinolytic activity were found in the tumor tissue. These phenomena were accompanied by a significant elevation in prolidase activity and an increase in beta(1) integrin expression in stomach cancer, compared to control tissue.


CONCLUSIONS
The data presented suggest an enhancement of collagen turnover in stomach cancer. It may be suggested that the increased degradation of collagen by gelatinase in cancer tissue is balanced by an increased biosynthesis of this protein.
Guszczyn
Tomasz
T
Department of Medical Biochemistry, Medical Academy of Białystok, ul. Mickiewicza 2, PL-15-089 Białystok, Poland. tombial@mp.pl
Sobolewski
Krzysztof
K
D015153:Blotting, Western; D002277:Carcinoma / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism*; D004150:Dipeptidases / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000503:physiopathology*
D019012:Integrin beta1; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline