Saleh Yousif, Siewiński Maciej, Kielan Wojciech, Ziółkowski Piotr, Gryboś Marian, Rybka Jacek
1st Department of Gynaecology and Obstetrics, Wroclaw Medical University, Wroclaw, Poland.
J Exp Ther Oncol. 2003 Nov-Dec;3(6):319-24. doi: 10.1111/j.1533-869x.2003.01105.x.
Degradation of the basement membrane and surrounding extracellular matrix is likely to represent a key step in cancer invasion and metastasis. The purpose of this study was to determine whether gastric cancer tissues demonstrate higher cysteine proteases activities: cathepsins B and L during cancer progression in compression with non-cancerous tissues.
We measured the expression of both cathepsins B and L in 30 patients with gastric cancer tissues and non-cancerous tissues activities by a fluorescence assay and immunohistochemical staining. We attempted to regulate cathepsin B and L expression using egg white cystatin.
The activities of cathepsins B and L were significantly higher in cancerous than in non-cancerous tissues (P </= 0.0001). Activities of these enzymes decreased 18-fold after treatment of tissue homogenates with 5 nM of purified egg white cystatin. Immunohistochemical staining was significant and positive expression of low molecular weight cystatin was observed on the tumor cell surface in gastric carcinoma. It was found that non-cancerous tissues (control) were not stained with anti-egg white antibody.
Our experiment demonstrated that the cysteine peptidases cathepsins B and L may be useful for the early detection of gastric cancer. The results suggest that addition of egg white cystatin reduces the activities of cathepsins B and L to that of non-cancerous values.
基底膜和周围细胞外基质的降解可能是癌症侵袭和转移的关键步骤。本研究的目的是确定在癌症进展过程中,与非癌组织相比,胃癌组织中半胱氨酸蛋白酶(组织蛋白酶B和L)的活性是否更高。
我们通过荧光测定和免疫组织化学染色,测量了30例胃癌组织和非癌组织中组织蛋白酶B和L的表达及活性。我们尝试用蛋清半胱氨酸蛋白酶抑制剂调节组织蛋白酶B和L的表达。
组织蛋白酶B和L在癌组织中的活性显著高于非癌组织(P≤0.0001)。用5 nM纯化的蛋清半胱氨酸蛋白酶抑制剂处理组织匀浆后,这些酶的活性降低了18倍。免疫组织化学染色显著,在胃癌肿瘤细胞表面观察到低分子量半胱氨酸蛋白酶抑制剂的阳性表达。发现非癌组织(对照)未被抗蛋清抗体染色。
我们的实验表明,半胱氨酸肽酶组织蛋白酶B和L可能有助于胃癌的早期检测。结果表明,添加蛋清半胱氨酸蛋白酶抑制剂可将组织蛋白酶B和L的活性降低至非癌组织的水平。