Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis
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Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis. / Ingvarsen, Signe Z.; Gardsvoll, Henrik; van Putten, Sander; Norregaard, Kirstine S.; Krigslund, Oliver; Meilstrup, Josephine A.; Tran, Collin; Jurgensen, Henrik J.; Melander, Maria C.; Nielsen, Carsten H.; Kjaer, Andreas; Bugge, Thomas H.; Engelholm, Lars H.; Behrendt, Niels.
I: Scientific Reports, Bind 10, Nr. 1, 19138, 2020, s. 1-16.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis
AU - Ingvarsen, Signe Z.
AU - Gardsvoll, Henrik
AU - van Putten, Sander
AU - Norregaard, Kirstine S.
AU - Krigslund, Oliver
AU - Meilstrup, Josephine A.
AU - Tran, Collin
AU - Jurgensen, Henrik J.
AU - Melander, Maria C.
AU - Nielsen, Carsten H.
AU - Kjaer, Andreas
AU - Bugge, Thomas H.
AU - Engelholm, Lars H.
AU - Behrendt, Niels
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - COLLAGEN DEGRADATION
KW - ORTHOTOPIC MODEL
KW - POOR-PROGNOSIS
KW - CANCER
KW - INVASION
KW - RECEPTOR
KW - EXPRESSION
KW - DEFICIENT
KW - PATHWAYS
U2 - 10.1038/s41598-020-75995-6
DO - 10.1038/s41598-020-75995-6
M3 - Journal article
C2 - 33154487
VL - 10
SP - 1
EP - 16
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19138
ER -
ID: 252038431