The serine protease matriptase inhibits migration and proliferation in multiple myeloma cells
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Ida Steiro1, Esten N. Vandsemb1, Samah Elsaadi1, Kristine Misund1, Anne-Marit Sponaas1, Magne Børset1,2, Pegah Abdollahi1,3 and Tobias S. Slørdahl1,4
1 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
2 Department of Immunology and Transfusion Medicine, St. Olav's University Hospital, Trondheim, Norway
3 Laboratory Clinic, St. Olav's University Hospital, Trondheim, Norway
4 Department of Hematology, St. Olav's University Hospital, Trondheim, Norway
Keywords: matriptase; multiple myeloma; tumor suppressor; migration; Src
Received: September 08, 2022 Accepted: October 12, 2022 Published: October 20, 2022
Background: 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.
Materials and Methods: 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 in vitro. By use of the CoMMpass database, we assessed the clinical relevance of matriptase in MM patients.
Results: Matriptase was expressed in 96% of patient samples and all HMCLs tested. Overexpression of matriptase in vitro reduced proliferation, and significantly decreased cytokine-induced migration. Conversely, matriptase knockdown significantly enhanced migration. Mechanistically, overexpression of matriptase inhibited activation of Src kinase.
Conclusions: Our findings may suggest a novel role of matriptase as a tumor suppressor in MM pathogenesis.
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