help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2007.070298 on September 6, 2007

Published online before print September 6, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2007.070298v1
171/4/1342    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klement, H.
Right arrow Articles by Rak, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klement, H.
Right arrow Articles by Rak, J.
(American Journal of Pathology. 2007;171:1342-1351.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070298

Atherosclerosis and Vascular Aging as Modifiers of Tumor Progression, Angiogenesis, and Responsiveness to Therapy

Halka Klement*{dagger}, Brad St. Croix{ddagger}, Chloe Milsom*, Linda May*, Qing Guo§, Joanne L. Yu*, Petr Klement*{dagger} and Janusz Rak*¶

From the Henderson Research Centre* and the Population Health Institute,§ McMaster University, Hamilton, Ontario, Canada; the Montreal Children’s Hospital Research Institute, McGill University, Montreal, Quebec, Canada; University of Veterinary and Pharmaceutical Sciences,{dagger} Brno, Czech Republic; and the National Cancer Institute at Frederick,{ddagger} Frederick, Maryland

It is rarely considered that age-related common vascular co-morbidities may affect therapeutic outcomes of antiangiogenic therapy in cancer. Indeed, the accepted model of human disease consists of 4- to 8-week-old (young) tumor-bearing, but otherwise healthy, experimental mice, yet human cancers are diagnosed and treated in later decades of life when atherosclerosis and vascular diseases are highly prevalent. Here we present evidence that tumor growth and angiogenesis are profoundly altered in mice affected by natural aging and with genetically induced atherosclerosis (in ApoE–/– mice). Thus, transplantable tumors (Lewis lung carcinoma and B16F1) grew at higher rates in young (4 to 8 weeks old) ApoE+/+ and ApoE–/– nonatherosclerotic syngeneic recipients than in their old (12 to 18 months old) or atherosclerotic (old/ApoE–/–) counterparts. These age-related changes were paralleled by reduced tumor vascularity, lower expression of tumor endothelial marker 1, increased acute tumor hypoxia, depletion of circulating CD45–/VEGFR+ cells, and impaired endothelial sprouting ex vivo. Exposure of tumor-bearing mice to metronomic therapy with cyclophosphamide exerted antimitotic effects on tumors in young hosts, but this effect was reduced in atherosclerotic mice. Collectively, our results suggest that vascular aging and disease may affect tumor progression, angiogenesis, and responses to therapy.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. Yu, L. May, C. Milsom, G. M. Anderson, J. I. Weitz, J. P. Luyendyk, G. Broze, N. Mackman, and J. Rak
Contribution of Host-Derived Tissue Factor to Tumor Neovascularization
Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1975 - 1981.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society for Investigative Pathology.