Ly6G+ inflammatory cells enable the conversion of cancer cells to cancer stem cells in an irradiated glioblastoma model

Cell Death and Differentiation
Hee-Young JeonHyunggee Kim

Abstract

Most glioblastomas frequently recur at sites of radiotherapy, but it is unclear if changes in the tumor microenvironment due to radiotherapy influence glioblastoma recurrence. Here, we demonstrate that radiation-induced senescent glioblastoma cells exhibit a senescence-associated secretory phenotype that functions through NFκB signaling to influence changes in the tumor microenvironment, such as recruitment of Ly6G+ inflammatory cells and vessel formation. In particular, Ly6G+ cells promote conversion of glioblastoma cells to glioblastoma stem cells (GSCs) through the NOS2-NO-ID4 regulatory axis. Specific inhibition of NFκB signaling in irradiated glioma cells using the IκBα super repressor prevents changes in the tumor microenvironment and dedifferentiation of glioblastoma cells. Treatment with Ly6G-neutralizing antibodies also reduces the number of GSCs and prolongs survival in tumor-bearing mice after radiotherapy. Clinically, a positive correlation exists between Ly6G+ cells and the NOS2-NO-ID4 regulatory axis in patients diagnosed with recurrent glioblastoma. Together, our results illustrate important roles for Ly6G+ inflammatory cells recruited by radiation-induced SASP in cancer cell dedifferentiation and tumor recurrence.

References

Oct 11, 1991·Journal of Neurosurgery·B C LiangH S Greenberg
Nov 19, 2004·Nature·Sheila K SinghPeter B Dirks
May 26, 2006·Nature Reviews. Cancer·Angelo L VescoviBrent A Reynolds
Aug 2, 2008·The New England Journal of Medicine·Patrick Y Wen, Santosh Kesari
Dec 4, 2009·Methods in Molecular Biology·Arthur Millius, Orion D Weiner
Dec 9, 2009·Molecular Oncology·Kristin SnipstadRuth H Paulssen
Jan 19, 2010·Annual Review of Pathology·Jean-Philippe CoppéJudith Campisi
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·G-One AhnJ Martin Brown
Mar 9, 2011·Journal of Medical Imaging and Radiation Oncology·Michael C DobelbowerJohn B Fiveash
Jul 28, 2011·International Journal of Cancer. Journal International Du Cancer·Stephanie M CabarcasWilliam L Farrar
Mar 15, 2012·Journal of Visualized Experiments : JoVE·Tamalee R Kramp, Kevin Camphausen
Apr 11, 2012·Stem Cells·Chann LagadecFrank Pajonk
Nov 13, 2012·Annual Review of Physiology·Judith Campisi
Mar 6, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Vincent PetitDidier Decaudin
Mar 23, 2013·Cancer Cell·Michele De Palma, Claire E Lewis
Oct 15, 2013·Cancer Research·David W InfangerClaudia Fischbach
Nov 10, 2013·Nature Medicine·Daniela F Quail, Johanna A Joyce
Nov 11, 2014·The Journal of Clinical Investigation·Evgeniy B EruslanovSunil Singhal
Dec 17, 2014·Archives of Pharmacal Research·Jun-Kyum KimHyunggee Kim
Jul 29, 2015·Advances in Cancer Research·Katherine H ParkerSuzanne Ostrand-Rosenberg
Nov 21, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hee-Young JeonHyunggee Kim
Feb 22, 2017·Biochemical and Biophysical Research Communications·Jun-Kyum KimHyunggee Kim
Oct 5, 2018·Radiation Oncology·Miljana TanićRadmila Janković

❮ Previous
Next ❯

Citations

Aug 4, 2020·Molecular Oncology·Chelsea Gerada, Kevin M Ryan
Dec 31, 2019·Stem Cells International·Jilan LiuFeng Jin
Mar 19, 2020·International Journal of Molecular Sciences·Sabbir KhanJohn F de Groot
Jan 6, 2021·International Journal of Molecular Sciences·Alexander OuNazanin Majd
Mar 12, 2021·Frontiers in Oncology·Yasaman IranmaneshChongran Sun

❮ Previous
Next ❯

Methods Mentioned

BETA
Transfection
fluorescence-activated cell sorting
xenograft
FACS
flow cytometry
surgical resection
RNA-seq

Software Mentioned

MetaMorph
GSEA

Related Concepts

Related Feeds

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Related Papers

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hee-Young JeonHyunggee Kim
Current Opinion in Clinical Nutrition and Metabolic Care
Yi ZhuJames L Kirkland
Oncoimmunology
Elvira CrescenziAntonio Leonardi
© 2022 Meta ULC. All rights reserved