Co‑localisation of intra‑nuclear membrane type‑1 matrix metalloproteinase and hypoxia inducible factor‑2α in osteosarcoma and prostate carcinoma cells

Chan,Corey D.; Haagensen,Emma J.; Tensaout,Hayeit A.; Rennie,Katherine J.; Gamie,Zakareya; Barry,James; Birch,Mark A.; Gerrand,Craig H.; Nisar,Sohail; Robson,Craig N.; Lunec,John; Rankin,Kenneth S.

doi:10.3892/ol.2020.12419

February-2021 Volume 21 Issue 2

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February-2021 Volume 21 Issue 2

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Co‑localisation of intra‑nuclear membrane type‑1 matrix metalloproteinase and hypoxia inducible factor‑2α in osteosarcoma and prostate carcinoma cells

Authors:
- Corey D. Chan
- Emma J. Haagensen
- Hayeit A. Tensaout
- Katherine J. Rennie
- Zakareya Gamie
- James Barry
- Mark A. Birch
- Craig H. Gerrand
- Sohail Nisar
- Craig N. Robson
- John Lunec
- Kenneth S. Rankin
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Affiliations: Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne NE2 4HH, UK, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK, Institute of Cellular Medicine, Musculoskeletal Research Group, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge University, Cambridge CB2 2QQ, UK, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex HA7 4LP, UK

Copyright: © Chan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 158
|
Published online on: December 31, 2020

https://doi.org/10.3892/ol.2020.12419
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Abstract

Increased membrane type‑1 matrix metalloproteinase (MT1‑MMP) expression in osteosarcoma is predictive of poor prognosis and directs bone metastasis in prostate carcinoma. MT1‑MMP subcellular localisation varies with oxygen tension, and, therefore, the aim of the present study was to assess protein interactions between MT1‑MMP and the hypoxia inducible factors (HIF‑1α and HIF‑2α). MT1‑MMP protein expression was investigated across a panel of cancer cell lines, including a positive and negative control. The hypoxia‑induced alteration in subcellular location of MT1‑MMP, HIF‑1α and HIF‑2α in the U2OS osteosarcoma cell line was assessed using subcellular fractionation. A proximity ligation assay was utilised to assess protein to protein interactions in the osteosarcoma U2OS and prostate carcinoma PC3 cell lines. U2OS and PC3 cells exhibited a significantly increased intra‑nuclear interaction between MT1‑MMP and HIF‑2α in response to hypoxia. The role of this warrants further investigation as it may unveil novel opportunities to target MT1‑MMP, which is of particular significance for osteosarcoma since current treatment options are limited.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Co‑localisation of intra‑nuclear membrane type‑1 matrix metalloproteinase and hypoxia inducible factor‑2α in osteosarcoma and prostate carcinoma cells

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