Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development.

Autor:	Luo X; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Fu Y; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Loza AJ; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Murali B; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Leahy KM; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Ruhland MK; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Gang M; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA., Su X; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Zamani A; Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Shi Y; Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Lavine KJ; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA., Ornitz DM; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Weilbaecher KN; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Long F; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Novack DV; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Faccio R; Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Longmore GD; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA., Stewart SA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; ICCE Institute, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: sheila.stewart@wustl.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Jan 05; Vol. 14 (1), pp. 82-92. Date of Electronic Publication: 2015 Dec 24.
DOI:	10.1016/j.celrep.2015.12.016
Abstrakt:	More than 85% of advanced breast cancer patients suffer from metastatic bone lesions, yet the mechanisms that facilitate these metastases remain poorly understood. Recent studies suggest that tumor-derived factors initiate changes within the tumor microenvironment to facilitate metastasis. However, whether stromal-initiated changes are sufficient to drive increased metastasis in the bone remains an open question. Thus, we developed a model to induce reactive senescent osteoblasts and found that they increased breast cancer colonization of the bone. Analysis of senescent osteoblasts revealed that they failed to mineralize bone matrix and increased local osteoclastogenesis, the latter process being driven by the senescence-associated secretory phenotype factor, IL-6. Neutralization of IL-6 was sufficient to limit senescence-induced osteoclastogenesis and tumor cell localization to bone, thereby reducing tumor burden. Together, these data suggest that a reactive stromal compartment can condition the niche, in the absence of tumor-derived signals, to facilitate metastatic tumor growth in the bone. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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