Mai Jianxin, Sameni Mansoureh, Mikkelsen Tom, Sloane Bonnie F
Department of Pharmacology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Biol Chem. 2002 Sep;383(9):1407-13. doi: 10.1515/BC.2002.159.
Degradation of extracellular matrix proteins by proteases such as the cysteine protease cathepsin B is critical to malignant progression. We have established that procathepsin B presents on the surface of tumor cells through its interaction with the annexin II tetramer [Mai et al., J. Biol. Chem. 275 (2000),12806-12812]. Cathepsin B activity can also be detected on the tumor cell surface and in their culture medium. Interestingly, the annexin II tetramer also interacts with extracellular matrix proteins, such as collagen I, fibrin and tenascin-C. Both cathepsin B and tenascin-C are expressed at high levels in malignant tumors, especially at the invasive edges of tumors, and are implicated in tumor angiogenesis. In this study, we report that tenascin-C can be degraded by cathepsin B in vitro. We demonstrate by immunohistochemistry that both cathepsin B and tenascin-C are expressed highly in malignant anaplastic astrocytomas and glioblastomas as compared to normal brain tissues. Interestingly, cathepsin B and tenascin-C were also detected in association with tumor neovessels. We suggest that interactions between cathepsin B and tenascin-C are involved in the progression of gliomas including the angiogenesis that is a hallmark of anaplastic astrocytomas.
诸如半胱氨酸蛋白酶组织蛋白酶B等蛋白酶对细胞外基质蛋白的降解作用对恶性进展至关重要。我们已经证实，组织蛋白酶原B通过与膜联蛋白II四聚体相互作用而存在于肿瘤细胞表面[Mai等人，《生物化学杂志》275 (2000)，12806 - 12812]。在肿瘤细胞表面及其培养基中也能检测到组织蛋白酶B的活性。有趣的是，膜联蛋白II四聚体还与细胞外基质蛋白相互作用，如I型胶原、纤维蛋白和腱生蛋白 - C。组织蛋白酶B和腱生蛋白 - C在恶性肿瘤中均高表达，尤其是在肿瘤的浸润边缘，并且与肿瘤血管生成有关。在本研究中，我们报道腱生蛋白 - C在体外可被组织蛋白酶B降解。我们通过免疫组织化学证明，与正常脑组织相比，组织蛋白酶B和腱生蛋白 - C在恶性间变性星形细胞瘤和胶质母细胞瘤中均高表达。有趣的是，在肿瘤新生血管中也检测到了组织蛋白酶B和腱生蛋白 - C。我们认为组织蛋白酶B与腱生蛋白 - C之间的相互作用参与了胶质瘤的进展，包括间变性星形细胞瘤的标志性特征——血管生成。
