Center for Myeloma Research, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Department of Immunology and Transfusion Medicine, St. Olav's University Hospital, Trondheim, Norway.
Oncotarget. 2022 Oct 20;13:1175-1186. doi: 10.18632/oncotarget.28300.
Multiple myeloma (MM) is an incurable malignancy of plasma cells. The serine protease matriptase is frequently dysregulated in human carcinomas, which facilitates tumor progression and metastatic dissemination. The importance of matriptase in hematological malignancies is yet to be clarified. In this study, we aimed to characterize the role of matriptase in MM.
mRNA expression of matriptase and its inhibitors hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 was studied in primary MM cells from patient samples and human myeloma cell lines (HMCLs). We further investigated the effect of matriptase on migration and proliferation of myeloma cells . By use of the CoMMpass database, we assessed the clinical relevance of matriptase in MM patients.
Matriptase was expressed in 96% of patient samples and all HMCLs tested. Overexpression of matriptase reduced proliferation, and significantly decreased cytokine-induced migration. Conversely, matriptase knockdown significantly enhanced migration. Mechanistically, overexpression of matriptase inhibited activation of Src kinase.
Our findings may suggest a novel role of matriptase as a tumor suppressor in MM pathogenesis.
多发性骨髓瘤（MM）是一种不可治愈的浆细胞恶性肿瘤。丝氨酸蛋白酶组织蛋白酶 H 在人类癌组织中经常失调，促进肿瘤的进展和转移扩散。组织蛋白酶 H 在血液恶性肿瘤中的重要性尚不清楚。在这项研究中，我们旨在研究组织蛋白酶 H 在 MM 中的作用。
研究了来自患者样本和人骨髓瘤细胞系（HMCL）的原代 MM 细胞中组织蛋白酶 H 及其抑制剂肝细胞生长因子激活抑制剂（HAI）-1 和 HAI-2 的 mRNA 表达。我们进一步研究了组织蛋白酶 H 对骨髓瘤细胞迁移和增殖的影响。通过使用 CoMMpass 数据库，我们评估了组织蛋白酶 H 在 MM 患者中的临床相关性。
组织蛋白酶 H 在 96%的患者样本和所有测试的 HMCL 中表达。组织蛋白酶 H 的过表达减少了增殖，并显著降低了细胞因子诱导的迁移。相反，组织蛋白酶 H 的敲低显著增强了迁移。在机制上，组织蛋白酶 H 的过表达抑制了Src 激酶的激活。
我们的发现可能表明组织蛋白酶 H 在 MM 发病机制中作为肿瘤抑制因子的新作用。
