The HERV-K accessory protein Np9 controls viability and migration of teratocarcinoma cells

Susana M. Chan, Tamar Sapir, Sung Soo Park, Jean François Rual, Rafael Contreras-Galindo, Orly Reiner, David M. Markovitz

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32 Scopus citations

Abstract

Human endogenous retroviruses are remnants of ancient germline infections that make up approximately 8% of the modern human genome. The HERV-K (HML-2) family is one of the most recent entrants into the human germline, these viruses appear to be transcriptionally active, and HERV-K viral like particles (VLPs) are found in cell lines from a number of human malignancies. HERV-K VLPs were first found to be produced in teratocarcinoma cell lines, and since then teratocarcinoma has been thought of as the classical model for HERVKs, with the NCCIT teratocarcinoma cell line particularly known to produce VLPs. Treatment for teratocarcinoma has progressed since its discovery, with improved prognosis for patients. Since the introduction of platinum based therapy, first year survival has greatly improved even with disseminated disease; however, it is estimated that 20% to 30% of patients present with metastatic germ cell tumor relapse following initial treatments. Also, the toxicity associated with the use of chemotherapeutic agents used to treat germ cell tumors is still a major concern. In this study, we show that the depletion of the HERV-K accessory protein Np9 increases the sensitivity of NCCIT teratocarcinoma cells to bleomycin and cisplatin. While decreasing the expression of Np9 had only a modest effect on the baseline viability of the cells, the reduced expression of Np9 increased the sensitivity of the teratocarcinoma cells to environmental (serum starvation) and chemical (chemotherapeutic) stresses. Np9 is also essential to the migration of NCCIT teratocarcinoma cells: in a wound closure assay, reduced expression of Np9 resulted in cells migrating into the wound at a slower rate, whereas reintroduction of Np9 resulted in NCCIT cells migrating back into the wound in a manner similar to the control. These findings support the implication that the HERV-K accessory protein Np9 has oncogenic potential.

Original languageEnglish (US)
Article numbere0212970
JournalPloS one
Volume14
Issue number2
DOIs
StatePublished - Feb 2019

Bibliographical note

Funding Information:
Funding:Thisworkwassupportedbythe UniversityofMichigan/IsraelPartnershipfor ResearchandEducation.J.F.R.andS.S.P.were supportedbytheNationalInstitutesofHealth(NIH) andNationalCancerInstitute(NCI)grant (R01CA187903).S.M.C.wassupportedby NationalInstitutesofHealth(NIH)grantsT32-GM007315and5T32GM008353-24.Thefunders hadnoroleinstudydesign,datacollectionand

Funding Information:
This work was supported by the University of Michigan/Israel Partnership for Research and Education. J.F.R. and S.S.P. were supported by the National Institutes of Health (NIH) and National Cancer Institute (NCI) grant (R01CA187903). S.M.C. was supported by National Institutes of Health (NIH) grants T32- GM007315 and 5T32GM008353-24.

Publisher Copyright:
© 2019 Chan et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

  • Antineoplastic Agents/pharmacology
  • Bleomycin/pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Cisplatin/pharmacology
  • Drug Resistance, Neoplasm
  • Endogenous Retroviruses/genetics
  • Gene Products, env/genetics
  • Humans
  • Male
  • Teratocarcinoma/pathology
  • Testicular Neoplasms/pathology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural

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