Enhanced prolidase activity and decreased collagen content in breast cancer tissue
Enhanced prolidase activity and decreased collagen content in breast cancer tissue
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DOI：
10.1111/j.1365-2613.2006.00486.x
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发表时间：
2006-08-01
影响因子：
3
通讯作者：
Wojtukiewicz, Marek Z.
中科院分区：
文献类型：
--
作者：
Cechowska-Pasko, Marzanna;Palka, Jerzy;Wojtukiewicz, Marek Z.
整合素与细胞外基质（ECM）蛋白之间的粘附相互作用在肿瘤发生和侵袭中起重要作用。ECM的主要成分是胶原蛋白，其在与整合素的相互作用中起核心作用。肿瘤细胞表达某些胶原酶（明胶酶）是所谓的转移表型的特征之一，可能是通过破坏ECM屏障以及改变ECM-细胞相互作用。虽然细胞外胶原酶启动胶原的分解，但胶原降解的最后一步是由细胞内脯氨酰二肽酶催化的。本文研究了7例可手术乳腺癌的胶原沉积、明胶分解酶和脯氨酰二肽酶活性、β（1）-整合素受体的表达及其可能的关系。在乳腺癌组织中，我们发现胶原蛋白的量显著减少。乳腺癌组织中胶原沉积的减少伴随着组织明胶分解和脯氨酰二肽酶活性的增加。同时，观察到乳腺癌组织中β（1）-整合素受体的表达略有下降。这些结果表明，乳腺癌组织中胶原代谢的改变可能反映了癌细胞侵袭性表型的特征性组织重塑。乳腺癌组织中明胶分解酶和脯氨酰二肽酶活性的增加可能会增强基质基质的降解，从而可能促进转移性播散。基于这些数据，似乎具有明胶分解和氨脯氨酸二肽酶抑制活性的化合物可以被认为是用于乳腺癌治疗的潜在候选药物。
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.