Tzimas George N, Chevet Eric, Jenna Sarah, Nguyên Duc Thang, Khatib Abdel M, Marcus Victoria, Zhang Yi, Chrétien Michel, Seidah Nabil, Metrakos Peter
Transplant and Hepato-Pancreatobiliary Research Group, McGill University Health Center, McGill University, S.10.26, Montreal, H3A1A1, Canada.
BMC Cancer. 2005 Nov 17;5:149. doi: 10.1186/1471-2407-5-149.
The family of proprotein convertases has been recently implicated in tumorigenesis and metastasis in animal models. However, these studies have not yet been completely corroborated in human tumors.
Using RT PCR, immunoblot and immunohistochemistry we assessed the presence and the processing patterns of the convertases PC1 and PC2 as well as the PC2 specific chaperone 7B2 in human liver metastases originating from colorectal cancer and compared them to unaffected and normal liver. Furthermore, we assessed the presence and processing profiles of PC1, PC2 and 7B2 in primary colon cancers.
mRNA, protein expression, and protein cleavage profiles of proprotein convertases 1 and 2 are altered in liver colorectal metastasis, compared to unaffected and normal liver. Active PC1 protein is overexpressed in tumor, correlating with its mRNA profile. Moreover, the enhanced PC2 processing pattern in tumor correlates with the overexpression of its specific binding protein 7B2. These results were corroborated by immunohistochemistry. The specific and uniform convertase pattern observed in the metastases was present only in a fraction of primary colon cancers.
The uniformly altered proprotein convertase profile in liver metastases is observed only in a fraction of primary colon cancers, suggesting possible selection processes involving PCs during metastasis as well as an active role of PCs in liver metastasis. In addition, the exclusive presence of 7B2 in metastatic tumors may represent a new target for early diagnosis, prognosis and/or treatment.
前蛋白转化酶家族最近在动物模型的肿瘤发生和转移中被认为有一定作用。然而，这些研究尚未在人类肿瘤中得到完全证实。
我们使用逆转录聚合酶链反应（RT PCR）、免疫印迹和免疫组织化学方法，评估了前蛋白转化酶PC1和PC2以及PC2特异性伴侣蛋白7B2在源自结直肠癌的人类肝转移灶中的存在情况和加工模式，并将其与未受影响的正常肝脏进行比较。此外，我们还评估了原发性结肠癌中PC1、PC2和7B2的存在情况和加工谱。
与未受影响的正常肝脏相比，前蛋白转化酶1和2的信使核糖核酸（mRNA）、蛋白质表达及蛋白质切割谱在肝结直肠癌转移灶中发生了改变。活性PC1蛋白在肿瘤中过度表达，与其mRNA谱相关。此外，肿瘤中PC2加工模式的增强与其特异性结合蛋白7B2的过度表达相关。这些结果通过免疫组织化学得到了证实。在转移灶中观察到的特异性且一致的转化酶模式仅在一部分原发性结肠癌中出现。
仅在一部分原发性结肠癌中观察到肝转移灶中前蛋白转化酶谱的一致改变，这表明在转移过程中可能存在涉及前蛋白转化酶的选择过程，以及前蛋白转化酶在肝转移中发挥的积极作用。此外，7B2仅在转移性肿瘤中的存在可能代表早期诊断、预后和/或治疗的新靶点。
