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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- Published online on: December 31, 2020 https://doi.org/10.3892/ol.2020.12419
- Article Number: 158
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Copyright: © Chan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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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.
