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PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells

A significant proportion of breast cancer patients develop bone metastases, but the mechanisms regulating tumor cell dissemination from the primary site to the skeleton remain largely unknown. Using a novel model of spontaneous bone metastasis derived from human ER+ MCF7 cells, molecular profiling r...

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Detalles Bibliográficos
Autores principales: Clements, Miranda E., Johnson, Rachelle W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007387/
https://www.ncbi.nlm.nih.gov/pubmed/31636389
http://dx.doi.org/10.1038/s41388-019-1064-3
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author Clements, Miranda E.
Johnson, Rachelle W.
author_facet Clements, Miranda E.
Johnson, Rachelle W.
author_sort Clements, Miranda E.
collection PubMed
description A significant proportion of breast cancer patients develop bone metastases, but the mechanisms regulating tumor cell dissemination from the primary site to the skeleton remain largely unknown. Using a novel model of spontaneous bone metastasis derived from human ER+ MCF7 cells, molecular profiling revealed increased PREX1 expression in a cell line established from bone-disseminated MCF7 cells (MCF7b), which were more migratory, invasive, and adhesive in vitro compared to parental MCF7 cells, and this phenotype was mediated by PREX1. MCF7b cells grew poorly in the primary tumor site when re-inoculated in vivo, suggesting these cells are primed to grow in the bone, and were enriched in skeletal sites of metastasis over soft tissue sites. Skeletal dissemination from the primary tumor was reversed with PREX1 knockdown, indicating that PREX1 is a key driver of spontaneous dissemination of tumor cells from the primary site to the bone marrow. In breast cancer patients, PREX1 levels are significantly increased in ER+ tumors and associated with invasive disease and distant metastasis. Together, these findings implicate PREX1 in spontaneous bone dissemination and provide a significant advance to the molecular mechanisms by which breast cancer cells disseminate from the primary tumor site to bone.
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spelling pubmed-70073872020-04-21 PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells Clements, Miranda E. Johnson, Rachelle W. Oncogene Article A significant proportion of breast cancer patients develop bone metastases, but the mechanisms regulating tumor cell dissemination from the primary site to the skeleton remain largely unknown. Using a novel model of spontaneous bone metastasis derived from human ER+ MCF7 cells, molecular profiling revealed increased PREX1 expression in a cell line established from bone-disseminated MCF7 cells (MCF7b), which were more migratory, invasive, and adhesive in vitro compared to parental MCF7 cells, and this phenotype was mediated by PREX1. MCF7b cells grew poorly in the primary tumor site when re-inoculated in vivo, suggesting these cells are primed to grow in the bone, and were enriched in skeletal sites of metastasis over soft tissue sites. Skeletal dissemination from the primary tumor was reversed with PREX1 knockdown, indicating that PREX1 is a key driver of spontaneous dissemination of tumor cells from the primary site to the bone marrow. In breast cancer patients, PREX1 levels are significantly increased in ER+ tumors and associated with invasive disease and distant metastasis. Together, these findings implicate PREX1 in spontaneous bone dissemination and provide a significant advance to the molecular mechanisms by which breast cancer cells disseminate from the primary tumor site to bone. 2019-10-21 2020-02 /pmc/articles/PMC7007387/ /pubmed/31636389 http://dx.doi.org/10.1038/s41388-019-1064-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Clements, Miranda E.
Johnson, Rachelle W.
PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title_full PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title_fullStr PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title_full_unstemmed PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title_short PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells
title_sort prex1 drives spontaneous bone dissemination of er+ breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007387/
https://www.ncbi.nlm.nih.gov/pubmed/31636389
http://dx.doi.org/10.1038/s41388-019-1064-3
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