GLIPR1 expression is reduced in multiple myeloma but is not a tumour suppressor in mice

PLoS One. 2020 Jan 29;15(1):e0228408. doi: 10.1371/journal.pone.0228408. eCollection 2020.

Abstract

Multiple myeloma, a plasma cell malignancy, is a genetically heterogeneous disease and the genetic factors that contribute to its development and progression remain to be fully elucidated. The tumour suppressor gene GLIPR1 has previously been shown to be deleted in approximately 10% of myeloma patients, to inhibit the development of plasma cell tumours in ageing mice and to have reduced expression levels in the plasma cells of patients with light-chain amyloidosis, a myeloma-related malignancy. Therefore, we hypothesised that GLIPR1 may have tumour suppressor activity in multiple myeloma. In this study, we demonstrate that plasma cell expression of GLIPR1 is reduced in the majority of myeloma patients and Glipr1 expression is lost in the 5TGM1 murine myeloma cell line. However, overexpression of GLIPR1 in a human myeloma cell line did not affect cell proliferation in vitro. Similarly, re-expression of Glipr1 in 5TGM1 cells did not significantly reduce their in vitro proliferation or in vivo growth in C57BL/KaLwRij mice. In addition, using CRISPR-Cas9 genome editing, we generated C57BL/Glipr1-/- mice and showed that loss of Glipr1 in vivo did not affect normal haematopoiesis or the development of monoclonal plasma cell expansions in these mice up to one year of age. Taken together, our results suggest that GLIPR1 is unlikely to be a potent tumour suppressor in multiple myeloma. However, it remains possible that the down-regulation of GLIPR1 may cooperate with other genetic lesions to promote the development of myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation*
  • Gene Editing
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Multiple Myeloma / genetics
  • Multiple Myeloma / pathology*
  • Neoplasm Proteins / genetics*
  • Neoplasm Transplantation
  • Nerve Tissue Proteins / genetics*

Substances

  • GLIPR1 protein, human
  • Glipr1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins

Grants and funding

This research was supported by a Cancer Council SA (https://www.cancersa.org.au) Grant (no. APP1087011) awarded to ACWZ. JEN was supported by a Veronika Sacco Clinical Cancer Research Fellowship from the Florey Medical Research Foundation, University of Adelaide (https://health.adelaide.edu.au/engage/philanthropy/florey-medical-research-foundation). KV was supported by an Early Career Cancer Research Fellowship from the Cancer Council SA Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.