PDF(Pubmed)
Abstract：
Prostasin and matriptase are extracellular membrane serine proteases with opposing effects in solid epithelial tumors. Matriptase is an oncoprotein that promotes tumor initiation and progression, and prostasin is a tumor suppressor that reduces tumor invasion and metastasis. Previous studies have shown that a subgroup of Burkitt lymphoma have high levels of ectopic matriptase expression but no prostasin. Reducing the matriptase level via small interfering RNAs in B lymphoma cells impeded tumor xenograft growth in mice. Here, we report a novel approach to matriptase regulation in B cancer cells by prostasin via exosomes to initiate a prostasin-matriptase protease activation cascade. The activation and shedding of matriptase were monitored by measuring its quantity and trypsin-like serine protease activity in conditioned media. Sustained activation of the protease cascade in the cells was achieved by the stable expression of prostasin. The B cancer cells with prostasin expression presented phenotypes consistent with its tumor suppressor role, such as reduced growth and increased apoptosis. Prostasin exosomes could be developed as an agent to initiate the prostasin-matriptase cascade for treating B lymphoma with further studies in animal models.
摘要：
前列腺素和间质蛋白酶是在实体上皮肿瘤中具有相反作用的细胞外膜丝氨酸蛋白酶。间质蛋白酶是一种促进肿瘤发生和进展的癌蛋白，prostasin是一种抑制肿瘤侵袭和转移的肿瘤抑制剂。先前的研究表明，伯基特淋巴瘤的一个亚组具有高水平的异位基质蛋白酶表达，但没有前列腺蛋白。通过B淋巴瘤细胞中的小干扰RNA降低间质蛋白酶水平阻碍了小鼠的肿瘤异种移植物生长。这里,我们报道了一种新的方法，通过前列腺蛋白通过外泌体启动前列腺蛋白-间质蛋白酶激活级联反应来调节B癌细胞中的间质蛋白酶。通过测量其数量和条件培养基中胰蛋白酶样丝氨酸蛋白酶活性来监测间质蛋白酶的活化和脱落。通过前列腺素的稳定表达实现了细胞中蛋白酶级联的持续激活。前列腺素表达的B癌细胞呈现与其肿瘤抑制作用一致的表型，如生长减少和细胞凋亡增加。通过在动物模型中的进一步研究，可以开发前列腺素外泌体作为启动前列腺素-间质蛋白酶级联反应的药物来治疗B淋巴瘤。
