Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Scientific Reports, Vol. 10, No. 1, 19138, 2020, p. 1-16.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ingvarsen, SZ, Gardsvoll, H, van Putten, S, Norregaard, KS, Krigslund, O, Meilstrup, JA, Tran, C, Jurgensen, HJ, Melander, MC, Nielsen, CH, Kjaer, A, Bugge, TH, Engelholm, LH & Behrendt, N 2020, 'Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis', Scientific Reports, vol. 10, no. 1, 19138, pp. 1-16. https://doi.org/10.1038/s41598-020-75995-6

APA

Ingvarsen, S. Z., Gardsvoll, H., van Putten, S., Norregaard, K. S., Krigslund, O., Meilstrup, J. A., Tran, C., Jurgensen, H. J., Melander, M. C., Nielsen, C. H., Kjaer, A., Bugge, T. H., Engelholm, L. H., & Behrendt, N. (2020). Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis. Scientific Reports, 10(1), 1-16. [19138]. https://doi.org/10.1038/s41598-020-75995-6

Vancouver

Ingvarsen SZ, Gardsvoll H, van Putten S, Norregaard KS, Krigslund O, Meilstrup JA et al. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis. Scientific Reports. 2020;10(1):1-16. 19138. https://doi.org/10.1038/s41598-020-75995-6

Author

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. / Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis. In: Scientific Reports. 2020 ; Vol. 10, No. 1. pp. 1-16.

Bibtex

@article{d40da69a69414cf88784fca0ea185376,
title = "Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis",
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.",
keywords = "COLLAGEN DEGRADATION, ORTHOTOPIC MODEL, POOR-PROGNOSIS, CANCER, INVASION, RECEPTOR, EXPRESSION, DEFICIENT, PATHWAYS",
author = "Ingvarsen, {Signe Z.} and Henrik Gardsvoll and {van Putten}, Sander and Norregaard, {Kirstine S.} and Oliver Krigslund and Meilstrup, {Josephine A.} and Collin Tran and Jurgensen, {Henrik J.} and Melander, {Maria C.} and Nielsen, {Carsten H.} and Andreas Kjaer and Bugge, {Thomas H.} and Engelholm, {Lars H.} and Niels Behrendt",
year = "2020",
doi = "10.1038/s41598-020-75995-6",
language = "English",
volume = "10",
pages = "1--16",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

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