title: Enhanced prolidase activity and decreased collagen content in breast cancer tissue.
abstract: Adherent interactions between integrins and extracellular matrix (ECM) proteins play an important role in tumorigenicity and invasiveness. The major component of ECM is collagen that plays a central role in the interaction with integrins. The expression of certain collagenases (gelatinases) by tumour cells is one of the characteristic features of the so-called metastatic phenotype, presumably by breaking down ECM barriers as well by altering the ECM-cell interaction. Although extracellular collagenases initiate the breakdown of collagen, the final step of collagen degradation is catalysed by intracellular prolidase. Collagen deposition, gelatinolytic and prolidase activities, expression of beta(1)-integrin receptor and their possible relationships were studied in seven operable breast cancer cases. In breast cancer tissue, we have found significant decrease in the amount of collagen. The decrease in collagen deposition in breast cancer tissue was accompanied by increase in the tissue gelatinolytic and prolidase activities. Simultaneously, a slight decrease in the expression of beta(1)-integrin receptor in breast cancer tissue was observed. These results suggest that alteration in collagen metabolism in breast cancer tissue may reflect tissue remodelling, characteristic for invasive phenotype of cancer cells. Increased gelatinolytic and prolidase activities in breast cancer tissue may enhance stromal matrix degradation and thus may promote metastatic dissemination. On the basis of the data, it seems that compounds endowed with gelatinolytic and prolidase inhibitory activities may be considered as a potential drug candidates for breast cancer therapy.
authors.affiliation: Department of Medical Biochemistry, Medical Academy of Białystok, Poland. mapasko@o2.pl
authors.forename: Marzanna
authors.initials: M
authors.lastname: Cechowska-Pasko
authors.forename: Jerzy
authors.initials: J
authors.lastname: Pałka
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
mesh_terms: D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D003094:Collagen / Q000032:analysis* / Q000378:metabolism; D004150:Dipeptidases / Q000032:analysis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9