Targeting disseminated estrogen-receptor-positive breast cancer cells in bone marrow

Oncogene
Johanna M BuschhausGary D Luker

Abstract

Estrogen receptor-positive (ER+) breast cancer can recur up to 20 years after initial diagnosis. Delayed recurrences arise from disseminated tumors cells (DTCs) in sites such as bone marrow that remain quiescent during endocrine therapy and subsequently proliferate to produce clinically detectable metastases. Identifying therapies that eliminate DTCs and/or effectively target cells transitioning to proliferation promises to reduce risk of recurrence. To tackle this problem, we utilized a 3D co-culture model incorporating ER+ breast cancer cells and bone marrow mesenchymal stem cells to represent DTCs in a bone marrow niche. 3D co-cultures maintained cancer cells in a quiescent, viable state as measured by both single-cell and population-scale imaging. Single-cell imaging methods for metabolism by fluorescence lifetime (FLIM) of NADH and signaling by kinases Akt and ERK revealed that breast cancer cells utilized oxidative phosphorylation and signaling by Akt to a greater extent both in 3D co-cultures and a mouse model of ER+ breast cancer cells in bone marrow. Using our 3D co-culture model, we discovered that combination therapies targeting oxidative phosphorylation via the thioredoxin reductase (TrxR) inhibitor, D9, and the Akt...Continue Reading

References

Sep 30, 2000·European Journal of Biochemistry·E S Arnér, A Holmgren
Aug 3, 2002·Nature Reviews. Cancer·Ann F ChambersIan C MacDonald
May 25, 2006·Annals of Medicine·Michiaki Kohno, Jacques Pouyssegur
Feb 13, 2008·Cell·Asako Sakaue-SawanoAtsushi Miyawaki
Jul 4, 2009·Cancer Cell·Xiang H-F ZhangJoan Massagué
May 26, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hagen KenneckeKaren Gelmon
Jun 1, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Kai BartkowiakKlaus Pantel
Jun 16, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria Soledad SosaJulio A Aguirre-Ghiso
May 23, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Geeta MehtaShuichi Takayama
Nov 3, 2012·Journal of Biomedical Optics·Alex J WalshMelissa C Skala
Jun 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yi ZhangMark G Erlander
Sep 21, 2013·Journal of Laboratory Automation·Stephen P CavnarShuichi Takayama
Apr 2, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Penelope D OttewellIngunn Holen
Jun 6, 2014·Annals of Medicine·Miriam MartiniEmilio Hirsch
Aug 1, 2014·Cancer Immunology Research·Rasha Abu-EidSamir N Khleif
Dec 18, 2014·Nature Chemical Biology·Samuel E Weinberg, Navdeep S Chandel
Apr 22, 2015·International Journal of Biological Sciences·Gang MaJianming Xu
May 2, 2015·The Journal of Clinical Investigation·Stefan GrossKlaus P Hoeflich
Jun 14, 2015·Journal of the National Cancer Institute·Gongda XueBrian A Hemmings
Sep 27, 2015·Neoplasia : an International Journal for Oncology Research·Stephen P CavnarGary D Luker
Jun 2, 2016·Cell Structure and Function·Gembu MaryuKazuhiro Aoki
Aug 2, 2016·Tomography : a Journal for Imaging Research·Stephen P CavnarGary D Luker
Sep 10, 2016·Cell Communication and Signaling : CCS·Catharina MelzerRalf Hass
Sep 25, 2017·Cell Chemical Biology·Alba LuengoMatthew G Vander Heiden
Oct 17, 2017·Methods in Molecular Biology·Johanna M BuschhausGary D Luker
Nov 9, 2017·The New England Journal of Medicine·Hongchao PanUNKNOWN EBCTCG
Mar 6, 2018·Immune Network·Emily L Yarosz, Cheong-Hee Chang
Mar 23, 2018·Endocrine-related Cancer·Berna C ÖzdemirCathrin Brisken
Mar 30, 2018·Free Radical Biology & Medicine·Valeria ScalconMaria Pia Rigobello
Apr 25, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shilpa ThakurJoanna Klubo-Gwiezdzinska
Jul 10, 2018·Tomography : a Journal for Imaging Research·Henry R HaleyGary D Luker
Aug 22, 2018·Current Osteoporosis Reports·D Brooke WidnerYusuke Shiozawa

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Citations

Mar 5, 2021·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jamal Majidpoor, Keywan Mortezaee
Apr 21, 2021·Nature Reviews. Clinical Oncology·Lorenz C HofbauerKlaus Pantel
Jun 3, 2021·Cancers·Nico Hinz, Manfred Jücker
Jun 18, 2021·Nano-micro Letters·Yuzhen OuyangMinghua Wu
Jul 3, 2021·Cancers·Fabrizio FontanaPatrizia Limonta
Jul 3, 2021·Journal of Clinical Medicine·Deepak K SinghJulio A Aguirre-Ghiso
Sep 21, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Namita MahadikRajkumar Banerjee

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Methods Mentioned

BETA
imaging techniques
bioluminescence imaging
xenograft
ISS
FACS
FCS

Software Mentioned

Fluoview
ISS VistaVision
MATLAB
GraphPad Prism
ISS
FCS Express
Olympus Fluoview
CellSens
Living Image

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