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Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis
Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various st...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Endocrine Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923403/ https://www.ncbi.nlm.nih.gov/pubmed/27184014 http://dx.doi.org/10.3803/EnM.2016.31.2.206 |
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author | Kang, Yibin |
author_facet | Kang, Yibin |
author_sort | Kang, Yibin |
collection | PubMed |
description | Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis. |
format | Online Article Text |
id | pubmed-4923403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Korean Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-49234032016-07-07 Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis Kang, Yibin Endocrinol Metab (Seoul) Review Article Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis. Korean Endocrine Society 2016-06 2016-05-13 /pmc/articles/PMC4923403/ /pubmed/27184014 http://dx.doi.org/10.3803/EnM.2016.31.2.206 Text en Copyright © 2016 Korean Endocrine Society http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Kang, Yibin Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title | Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title_full | Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title_fullStr | Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title_full_unstemmed | Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title_short | Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis |
title_sort | dissecting tumor-stromal interactions in breast cancer bone metastasis |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923403/ https://www.ncbi.nlm.nih.gov/pubmed/27184014 http://dx.doi.org/10.3803/EnM.2016.31.2.206 |
work_keys_str_mv | AT kangyibin dissectingtumorstromalinteractionsinbreastcancerbonemetastasis |