A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma1 (original) (raw)
Journal Article
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
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Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
Search for other works by this author on:
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
Search for other works by this author on:
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
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Pediatric Hemato-Oncology Department, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University
,
Tel-Hashomer
,
Israel
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Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
Search for other works by this author on:
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences and The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University
,
Tel Aviv
,
Israel
Address correspondence and reprint requests to Dr. Adit Ben-Baruch, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel-Aviv 69978, Israel. E-mail: [email protected]
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Published:
15 October 2001
Cite
Hila Geminder, Orit Sagi-Assif, Lilach Goldberg, Tsipi Meshel, Gideon Rechavi, Isaac P Witz, Adit Ben-Baruch, A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma, The Journal of Immunology, Volume 167, Issue 8, October 2001, Pages 4747–4757, https://doi.org/10.4049/jimmunol.167.8.4747
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Abstract
The homing of hemopoietic stem cells to the bone marrow is mediated by specific interactions occurring between CXCR4, which is expressed on hemopoietic stem cells, and its ligand, stromal cell-derived factor-1 (SDF-1), a CXC chemokine secreted by bone marrow stromal cells. In the present study we evaluated the possibility that neuroblastoma cells use a mechanism similar to that used by hemopoietic stem cells to home to the bone marrow and adhere to bone marrow stromal cells. Our study suggests that CXCR4 expression may be a general characteristic of neuroblastoma cells. SH-SY5Y neuroblastoma cells express not only CXCR4, but also its ligand, SDF-1. CXCR4 expression on SH-SY5Y neuroblastoma cells is tightly regulated by tumor cell-derived SDF-1, as demonstrated by the ability of neutralizing Abs against human SDF-1α to up-regulate CXCR4 expression on the tumor cells. The reduction in CXCR4 expression following short term exposure to recombinant human SDF-1α can be recovered as a result of de novo receptor synthesis. Recombinant human SDF-1α induces the migration of CXCR4-expressing SH-SY5Y neuroblastoma cells in CXCR4- and heterotrimeric G protein-dependent manners. Furthermore, SH-SY5Y cells interact at multiple levels with bone marrow components, as evidenced by the fact that bone marrow-derived constituents promote SH-SY5Y cell migration, adhesion to bone marrow stromal cells, and proliferation. These results suggest that SH-SY5Y neuroblastoma cells are equipped with adequate machinery to support their homing to the bone marrow. Therefore, the ability of neuroblastoma tumors to preferentially form metastases in the bone marrow may be influenced by a set of complex CXCR4-SDF-1 interactions.
Copyright © 2001 by The American Association of Immunologists
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