Cargando…

Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow

Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenv...

Descripción completa

Detalles Bibliográficos
Autores principales: Funari, Alessia, Alimandi, Maurizio, Pierelli, Luca, Pino, Valentina, Gentileschi, Stefano, Sacchetti, Benedetto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627911/
https://www.ncbi.nlm.nih.gov/pubmed/31159336
http://dx.doi.org/10.3390/cancers11060763
_version_ 1783434843943600128
author Funari, Alessia
Alimandi, Maurizio
Pierelli, Luca
Pino, Valentina
Gentileschi, Stefano
Sacchetti, Benedetto
author_facet Funari, Alessia
Alimandi, Maurizio
Pierelli, Luca
Pino, Valentina
Gentileschi, Stefano
Sacchetti, Benedetto
author_sort Funari, Alessia
collection PubMed
description Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenvironment (HME) generating humanized bone/BM ossicles. To create a mouse model of hematogenous metastasis of human prostate cancer (PC) cells to human bone/BM, we injected PC cells in the blood circulatory system of Severe Combined Immunodeficiency (SCID)/beige mice bearing heterotopic ossicles. Results indicate that PC cells could efficiently home to mice-implanted extraskeletal BM ossicles, but were not able to colonize mice skeletal segments. In humanized bone/BM ossicles, early foci of PC cells occupied a perisinusoidal position, in close contact with perivascular stromal cells. These findings demonstrate the importance of the SSC compartment in recreating a suitable environment to metastatic PC cells. Our data support the hypothesis that BM SSCs committed to a pericyte fate can specify for homing niches of PC cells, suggesting an involvement of specific interactions with subendothelial stromal cells in extravasation of circulating metastatic PC cells to BM.
format Online
Article
Text
id pubmed-6627911
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-66279112019-07-23 Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow Funari, Alessia Alimandi, Maurizio Pierelli, Luca Pino, Valentina Gentileschi, Stefano Sacchetti, Benedetto Cancers (Basel) Article Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenvironment (HME) generating humanized bone/BM ossicles. To create a mouse model of hematogenous metastasis of human prostate cancer (PC) cells to human bone/BM, we injected PC cells in the blood circulatory system of Severe Combined Immunodeficiency (SCID)/beige mice bearing heterotopic ossicles. Results indicate that PC cells could efficiently home to mice-implanted extraskeletal BM ossicles, but were not able to colonize mice skeletal segments. In humanized bone/BM ossicles, early foci of PC cells occupied a perisinusoidal position, in close contact with perivascular stromal cells. These findings demonstrate the importance of the SSC compartment in recreating a suitable environment to metastatic PC cells. Our data support the hypothesis that BM SSCs committed to a pericyte fate can specify for homing niches of PC cells, suggesting an involvement of specific interactions with subendothelial stromal cells in extravasation of circulating metastatic PC cells to BM. MDPI 2019-05-31 /pmc/articles/PMC6627911/ /pubmed/31159336 http://dx.doi.org/10.3390/cancers11060763 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Funari, Alessia
Alimandi, Maurizio
Pierelli, Luca
Pino, Valentina
Gentileschi, Stefano
Sacchetti, Benedetto
Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title_full Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title_fullStr Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title_full_unstemmed Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title_short Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow
title_sort human sinusoidal subendothelial cells regulate homing and invasion of circulating metastatic prostate cancer cells to bone marrow
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627911/
https://www.ncbi.nlm.nih.gov/pubmed/31159336
http://dx.doi.org/10.3390/cancers11060763
work_keys_str_mv AT funarialessia humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow
AT alimandimaurizio humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow
AT pierelliluca humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow
AT pinovalentina humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow
AT gentileschistefano humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow
AT sacchettibenedetto humansinusoidalsubendothelialcellsregulatehomingandinvasionofcirculatingmetastaticprostatecancercellstobonemarrow