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Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment
Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM microenvir...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312379/ https://www.ncbi.nlm.nih.gov/pubmed/27517491 http://dx.doi.org/10.18632/oncotarget.11115 |
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author | Selleri, Carmine Montuori, Nunzia Salvati, Annamaria Serio, Bianca Pesapane, Ada Ricci, Patrizia Gorrasi, Anna Santi, Anna Li Hoyer-Hansen, Gunilla Ragno, Pia |
author_facet | Selleri, Carmine Montuori, Nunzia Salvati, Annamaria Serio, Bianca Pesapane, Ada Ricci, Patrizia Gorrasi, Anna Santi, Anna Li Hoyer-Hansen, Gunilla Ragno, Pia |
author_sort | Selleri, Carmine |
collection | PubMed |
description | Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM microenvironment. uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88-92). We previously reported the involvement of soluble uPAR in HSC mobilization. We now investigate its possible role in HSC homing and engraftment. We show similar levels of circulating full-length suPAR in healthy donors and in acute myeloid leukemia (AML) patients before and after the pre-transplant conditioning regimen. By contrast, levels of circulating DIIDIII-suPAR in AML patients are higher as compared to controls and significantly decrease after the conditioning. We found that suPAR and uPAR(84-95), a uPAR-derived peptide which mimics active DIIDIII-suPAR, induce a significant increase in Long Term Culture (LTC)-Initiating Cells (ICs) and in the release of clonogenic progenitors from LTCs of CD34(+) HSCs. Further, suPAR increases adhesion and survival of CD34(+) KG1 AML cells, whereas uPAR(84-95) increases their proliferation. Thus, circulating DIIDIII-suPAR, strongly increased in HSC mobilization, is indeed down-regulated by pre-transplant conditioning, probably to favour HSC homing. BM full-length suPAR and DIIDIII-suPAR may be involved in HSC lodgement within the BM by contributing to a suitable microenvironment. |
format | Online Article Text |
id | pubmed-5312379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53123792017-03-06 Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment Selleri, Carmine Montuori, Nunzia Salvati, Annamaria Serio, Bianca Pesapane, Ada Ricci, Patrizia Gorrasi, Anna Santi, Anna Li Hoyer-Hansen, Gunilla Ragno, Pia Oncotarget Research Paper Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM microenvironment. uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88-92). We previously reported the involvement of soluble uPAR in HSC mobilization. We now investigate its possible role in HSC homing and engraftment. We show similar levels of circulating full-length suPAR in healthy donors and in acute myeloid leukemia (AML) patients before and after the pre-transplant conditioning regimen. By contrast, levels of circulating DIIDIII-suPAR in AML patients are higher as compared to controls and significantly decrease after the conditioning. We found that suPAR and uPAR(84-95), a uPAR-derived peptide which mimics active DIIDIII-suPAR, induce a significant increase in Long Term Culture (LTC)-Initiating Cells (ICs) and in the release of clonogenic progenitors from LTCs of CD34(+) HSCs. Further, suPAR increases adhesion and survival of CD34(+) KG1 AML cells, whereas uPAR(84-95) increases their proliferation. Thus, circulating DIIDIII-suPAR, strongly increased in HSC mobilization, is indeed down-regulated by pre-transplant conditioning, probably to favour HSC homing. BM full-length suPAR and DIIDIII-suPAR may be involved in HSC lodgement within the BM by contributing to a suitable microenvironment. Impact Journals LLC 2016-08-08 /pmc/articles/PMC5312379/ /pubmed/27517491 http://dx.doi.org/10.18632/oncotarget.11115 Text en Copyright: © 2016 Selleri et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Selleri, Carmine Montuori, Nunzia Salvati, Annamaria Serio, Bianca Pesapane, Ada Ricci, Patrizia Gorrasi, Anna Santi, Anna Li Hoyer-Hansen, Gunilla Ragno, Pia Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title | Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title_full | Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title_fullStr | Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title_full_unstemmed | Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title_short | Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
title_sort | involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312379/ https://www.ncbi.nlm.nih.gov/pubmed/27517491 http://dx.doi.org/10.18632/oncotarget.11115 |
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