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Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow
Yusuke Shiozawa, … , Kenneth J. Pienta, Russell S. Taichman
Yusuke Shiozawa, … , Kenneth J. Pienta, Russell S. Taichman
Published March 23, 2011
Citation Information: J Clin Invest. 2011;121(4):1298-1312. https://doi.org/10.1172/JCI43414.
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Research Article Article has an altmetric score of 15

Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow

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Abstract

HSC homing, quiescence, and self-renewal depend on the bone marrow HSC niche. A large proportion of solid tumor metastases are bone metastases, known to usurp HSC homing pathways to establish footholds in the bone marrow. However, it is not clear whether tumors target the HSC niche during metastasis. Here we have shown in a mouse model of metastasis that human prostate cancer (PCa) cells directly compete with HSCs for occupancy of the mouse HSC niche. Importantly, increasing the niche size promoted metastasis, whereas decreasing the niche size compromised dissemination. Furthermore, disseminated PCa cells could be mobilized out of the niche and back into the circulation using HSC mobilization protocols. Finally, once in the niche, tumor cells reduced HSC numbers by driving their terminal differentiation. These data provide what we believe to be the first evidence that the HSC niche serves as a direct target for PCa during dissemination and plays a central role in bone metastases. Our work may lead to better understanding of the molecular events involved in bone metastases and new therapeutic avenues for an incurable disease.

Authors

Yusuke Shiozawa, Elisabeth A. Pedersen, Aaron M. Havens, Younghun Jung, Anjali Mishra, Jeena Joseph, Jin Koo Kim, Lalit R. Patel, Chi Ying, Anne M. Ziegler, Michael J. Pienta, Junhui Song, Jingcheng Wang, Robert D. Loberg, Paul H. Krebsbach, Kenneth J. Pienta, Russell S. Taichman

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Figure 3

HSCs and PCa cells colocalize to BM niches through Runx2.

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HSCs and PCa cells colocalize to BM niches through Runx2.
(A) To determi...
(A) To determine whether metastatic cells and HSC colocalize to the same niche, a confocal microscope was used to track prelabeled LSK HSCs (red) and prelabeled PCa cells (green) 24 hours after transplantation. Nuclei were stained with DAPI (blue). DIC, differential image contrast. (B–D) SCID mice were implanted with PCa cells. After 3 weeks, the long bones were collected. Representative elements of the BM were triple-stained with (B) anti-HLA antibodies, anti-Runx2 antibodies, and DAPI; (C) anti-CD150 antibodies, anti-lineage antibody cocktail, and anti-Runx2 antibodies; and (D) anti-CD150 antibodies, anti-lineage antibody cocktail, and anti-HLA antibodies. Arrows denote colocalization of HSCs and PCa cells (A and D), osteoblasts and PCa cells (B), or osteoblasts and HSCs (C). Original magnification, ×60. Scale bars: 10 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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