Host age is a systemic regulator of gene expression impacting cancer progression

Cancer Research
Afshin BeheshtiLynn Hlatky

Abstract

Aging is the major determinant of cancer incidence, which, in turn, is likely dictated in large part by processes that influence the progression of early subclinical (occult) cancers. However, there is little understanding of how aging informs changes in aggregate host signaling that favor cancer progression. In this study, we provide direct evidence that aging can serve as an organizing axis to define cancer progression-modulating processes. As a model system to explore this concept, we employed adolescent (68 days), young adult (143 days), middle-aged (551 days), and old (736 days) C57BL/6 mice as syngeneic hosts for engraftment of Lewis lung cancer to identify signaling and functional processes varying with host age. Older hosts exhibited dysregulated angiogenesis, metabolism, and apoptosis, all of which are associated with cancer progression. TGFβ1, a central player in these systemic processes, was downregulated consistently in older hosts. Our findings directly supported the conclusion of a strong host age dependence in determining the host tumor control dynamic. Furthermore, our results offer initial mechanism-based insights into how aging modulates tumor progression in ways that may be actionable for therapy or prevention.

References

Mar 1, 1975·Journal of Gerontology·I Kunstyr, H G Leuenberger
Sep 7, 1994·Journal of the National Cancer Institute·R PiliA Passaniti
Aug 6, 2000·Cell and Tissue Research·Y Higami, I Shimokawa
Jun 20, 2002·Journal of the National Cancer Institute·Lynn HlatkyJudah Folkman
Jul 16, 2003·Radiation Research·Bruce A CarnesDavid Hoel
Jun 10, 2005·The FEBS Journal·Farid RahimiCarolyn L Geczy
Feb 16, 2006·Mechanisms of Ageing and Development·Tatiana KaptzanJudith Leibovici
Jun 24, 2006·Nature Reviews. Cancer·Brian Bierie, Harold L Moses
Aug 31, 2006·Methods in Enzymology·Alexander I SaeedJohn Quackenbush
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·May J ReedStephen Plymate
Jan 25, 2007·Cell Cycle·Catherine GatzaLawrence A Donehower
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ljubov SimsonChristopher R Parish
Sep 14, 2007·Breast Cancer Research : BCR·Christina YauChristopher C Benz
Feb 26, 2008·Cell·Derrick J RossiIrving L Weissman
Jun 4, 2008·Cancer Research·Charles HardingRichard Wilson
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Jul 18, 2008·Nature Reviews. Cancer·Craig MurdochClaire E Lewis
Sep 27, 2008·The Journal of Investigative Dermatology·Davina A LewisDan F Spandau
Nov 6, 2009·Cancer Research·Heiko EnderlingPhilip Hahnfeldt
Feb 16, 2010·Cardiovascular Research·Alicia G Arroyo, M Luisa Iruela-Arispe
Mar 13, 2010·Disease Models & Mechanisms·Nor E SounniLisa M Coussens
Sep 3, 2010·Cold Spring Harbor Perspectives in Biology·Harold Moses, Mary Helen Barcellos-Hoff
Oct 16, 2010·Toxicology and Industrial Health·Charles HardingRichard Wilson
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 3, 2011·Journal of Mammary Gland Biology and Neoplasia·Mary Helen Barcellos-Hoff
May 19, 2011·Journal of Mammary Gland Biology and Neoplasia·David H NguyenMary Helen Barcellos-Hoff
Aug 24, 2012·Nature Reviews. Molecular Cell Biology·Tobias SperkaK Lenhard Rudolph
Nov 13, 2012·Annual Review of Physiology·Judith Campisi
Jan 12, 2013·Journal of Cellular and Molecular Medicine·Rui-An WangRutao Cui
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer

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Citations

Aug 11, 2015·Life Sciences in Space Research·Mary Helen Barcellos-HoffMichael M Weil
Nov 26, 2015·PLoS Computational Biology·Etienne BaratchartWilfried Souleyreau
Jul 13, 2019·Journal of Surgical Oncology·Francesco LonderoSandro Gelsomino
Jan 21, 2017·PloS One·Afshin BeheshtiAndrew M Evens
Jan 29, 2019·Frontiers in Oncology·Anatoly V Lichtenstein
Aug 28, 2019·British Journal of Haematology·Frank C PasseroAndrew M Evens
Nov 8, 2017·The Breast Journal·Elena ShagisultanovaAnthony D Elias
Oct 14, 2021·Journal for Immunotherapy of Cancer·Cangang ZhangBaojun Zhang

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