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Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases
Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827388/ https://www.ncbi.nlm.nih.gov/pubmed/31597373 http://dx.doi.org/10.3390/cancers11101507 |
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author | Ginter, Paula S. Karagiannis, George S. Entenberg, David Lin, Yu Condeelis, John Jones, Joan G. Oktay, Maja H. |
author_facet | Ginter, Paula S. Karagiannis, George S. Entenberg, David Lin, Yu Condeelis, John Jones, Joan G. Oktay, Maja H. |
author_sort | Ginter, Paula S. |
collection | PubMed |
description | Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional “doorways” for hematogenous dissemination. Here, we studied a well-annotated case–control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels. |
format | Online Article Text |
id | pubmed-6827388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68273882019-11-18 Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases Ginter, Paula S. Karagiannis, George S. Entenberg, David Lin, Yu Condeelis, John Jones, Joan G. Oktay, Maja H. Cancers (Basel) Article Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional “doorways” for hematogenous dissemination. Here, we studied a well-annotated case–control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels. MDPI 2019-10-08 /pmc/articles/PMC6827388/ /pubmed/31597373 http://dx.doi.org/10.3390/cancers11101507 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 Ginter, Paula S. Karagiannis, George S. Entenberg, David Lin, Yu Condeelis, John Jones, Joan G. Oktay, Maja H. Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title | Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title_full | Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title_fullStr | Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title_full_unstemmed | Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title_short | Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases |
title_sort | tumor microenvironment of metastasis (tmem) doorways are restricted to the blood vessel endothelium in both primary breast cancers and their lymph node metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827388/ https://www.ncbi.nlm.nih.gov/pubmed/31597373 http://dx.doi.org/10.3390/cancers11101507 |
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