Oncotarget | The Serine Protease Matriptase Inhibits Migration and Proliferation in Multiple Myeloma Cells

“We demonstrate that matriptase overexpression in vitro was associated with reduced myeloma cell proliferation and that matriptase significantly inhibited myeloma cell migration.”

BUFFALO, NY- November 7, 2022 – A new research paper was published in Oncotarget's Volume 13 on October 20, 2022, entitled, “The serine protease matriptase inhibits migration and proliferation in multiple myeloma cells.”

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, researchers Ida Steiro, Esten N. Vandsemb, Samah Elsaadi, Kristine Misund, Anne-Marit Sponaas, Magne Børset, Pegah Abdollahi, and Tobias S. Slørdahl from the Norwegian University of Science and Technology and St. Olav's University Hospital aimed to characterize the role of matriptase in MM.

“In this study, we investigated the functional role of matriptase in vitro using human multiple myeloma cells as a model system. We also explored the clinical relevance of matriptase expression using the publicly available MMRF CoMMpass dataset. Our findings may indicate a novel role of matriptase in MM pathogenesis.”

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). The researchers further investigated the effect of matriptase on migration and proliferation of myeloma cells in vitro. By use of the CoMMpass database, they assessed the clinical relevance of matriptase in MM patients.

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.

“Our findings may suggest a novel role of matriptase as a tumor suppressor in MM pathogenesis.”

DOI: https://doi.org/10.18632/oncotarget.28300 

Correspondence to: Ida Steiro - ida.j.steiro@ntnu.no 

Keywords: matriptase, multiple myeloma, tumor suppressor, migration, Src

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