Author:
Ingvarsen Signe Z.,Gårdsvoll Henrik,van Putten Sander,Nørregaard Kirstine S.,Krigslund Oliver,Meilstrup Josephine A.,Tran Collin,Jürgensen Henrik J.,Melander Maria C.,Nielsen Carsten H.,Kjaer Andreas,Bugge Thomas H.,Engelholm Lars H.,Behrendt Niels
Abstract
Abstract
The membrane-anchored matrix metalloprotease MT1-MMP is a potent collagenolytic enzyme with a well-established role in extracellular matrix turnover and cellular invasion into collagen-rich tissues. MT1-MMP is highly expressed in various types of cancer and has been demonstrated to be directly involved in several stages of tumor progression, including primary tumor growth, angiogenesis, invasion and metastasis. Osteosarcoma is the most common type of primary bone cancer. This disease is characterized by invasive tumor growth, leading to extensive bone destruction, and metastasis to the lungs. The tumor cells in human osteosarcoma display a strong expression of MT1-MMP, but the role of MT1-MMP in osteosarcoma progression is currently unknown. In this study, we investigated the role of MT1-MMP during various stages of osteosarcoma development. We utilized an optimized orthotopic murine osteosarcoma model and human osteosarcoma cells in which the MT1-MMP gene was knocked out using CRISPR/Cas9. We observed a strong expression of MT1-MMP in wildtype cells of both primary tumors and lung metastases, but, surprisingly, MT1-MMP deficiency did not affect primary tumor growth, bone degradation or the formation and growth of lung metastases. We therefore propose that, unlike findings reported in other cancers, tumor-expressed MT1-MMP is dispensable for all stages of osteosarcoma progression.
Funder
the Intramural Research Program at the National Institute of Dental and Craniofacial Research, NIH, USA
the Danish Medical Research Council
the Danish Cancer Society
The Novo Nordisk Foundation
Krista and Viggo Petersen’s Foundation
The Research Foundation of the Danish Capital Region
Publisher
Springer Science and Business Media LLC
Cited by
14 articles.
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