TY - JOUR
T1 - GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche
AU - Shiozawa, Yusuke
AU - Pedersen, Elisabeth A.
AU - Patel, Lalit R.
AU - Ziegler, Anne M.
AU - Havens, Aaron M.
AU - Jung, Younghun
AU - Wang, Jingcheng
AU - Zalucha, Stephanie
AU - Loberg, Robert D.
AU - Pienta, Kenneth J.
AU - Taichman, Russell S.
N1 - Funding Information:
Address all correspondence to: Russell S. Taichman, DMD, DMSc, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Room 3307, 1011 North University Ave, Ann Arbor, MI 48109-1078. E-mail: rtaich@umich.edu 1This work is directly supported by the Charles Eliot Ware Memorial Fellowship (A.M.H.), the Pediatric Oncology Research Fellowship (Y.S.), the National Cancer Institute (K.J.P. and R.S.T.), the Department of Defense (K.J.P. and R.S.T.), and the Prostate Cancer Foundation (K.J.P. and R.S.T.). K.J.P. receives support as an American Cancer Society Clinical Research Professor. 2This article refers to supplementary material, which is designated by Figure W1 and is available online at www.neoplasia.com. Received 15 August 2009; Revised 5 November 2009; Accepted 11 November 2009 Copyright © 2010 Neoplasia Press, Inc. All rights reserved 1522-8002/10/$25.00 DOI 10.1593/neo.91384
PY - 2010/2
Y1 - 2010/2
N2 - Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bone marrow. The role of the niche is thought to be the induction and sustenance of HSC dormancy. If metastatic PCa cells occupy a similar or the same ecological niche as HSCs, then it is likely that the initial role of the HSC niche will be to induce dormancy in metastatic cells. In this study, we demonstrate that the binding of PCa to annexin II induces the expression of the growth arrest-specific 6 (GAS6) receptors AXL, Sky, and Mer, which, in the hematopoietic system, induce dormancy. In addition, GAS6 produced by osteoblasts prevents PCa proliferation and protects PCa from chemotherapy-induced apoptosis. Our results suggest that the activation of GAS6 receptors on PCa in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy.
AB - Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bone marrow. The role of the niche is thought to be the induction and sustenance of HSC dormancy. If metastatic PCa cells occupy a similar or the same ecological niche as HSCs, then it is likely that the initial role of the HSC niche will be to induce dormancy in metastatic cells. In this study, we demonstrate that the binding of PCa to annexin II induces the expression of the growth arrest-specific 6 (GAS6) receptors AXL, Sky, and Mer, which, in the hematopoietic system, induce dormancy. In addition, GAS6 produced by osteoblasts prevents PCa proliferation and protects PCa from chemotherapy-induced apoptosis. Our results suggest that the activation of GAS6 receptors on PCa in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy.
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U2 - 10.1593/neo.91384
DO - 10.1593/neo.91384
M3 - Article
C2 - 20126470
AN - SCOPUS:76749109371
SN - 1522-8002
VL - 12
SP - 116
EP - 127
JO - Neoplasia
JF - Neoplasia
IS - 2
ER -