Hematogenous Dissemination of Breast Cancer Cells From Lymph Nodes Is Mediated by Tumor MicroEnvironment of Metastasis Doorways.
blood vessel
breast cancer
cancer cell dissemination
lymph node
lymphatic vessel
tumor microenvironment of metastasis (TMEM)
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
06
2020
accepted:
17
09
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
17
11
2020
Statut:
epublish
Résumé
In primary breast tumors, cancer cells hematogenously disseminate through doorways in the vasculature composed of three-cell complexes (known as Tumor MicroEnvironment of Metastasis) comprising a perivascular macrophage, a tumor cell overexpressing the actin-regulatory protein Mammalian Enabled (Mena), and an endothelial cell, all in direct physical contact. It has been previously shown that once tumor cells establish lymph node metastases in patients, TMEM doorways form in the metastatic tumor cell nests. However, it has not been established if such lymph node-TMEM doorways actively transit tumor cells into the peripheral circulation and on to tertiary sites. To address this question in this short report, we used a mouse model of lymph node metastasis to demonstrate that TMEM doorways: (1) exist in tumor-positive lymph nodes of mice, (2) are restricted to the blood vascular endothelium, (3) serve as a mechanism for further dissemination to peripheral sites such as to the lungs, and (4) their activity can be abrogated by a pharmaceutical intervention. Our data suggest that cancer cell dissemination via TMEM doorways is a common mechanism of breast cancer cell dissemination to distant sites and thus the pharmacological targeting of TMEM may be necessary, even after resection of the primary tumor, to suppress cancer cell dissemination.
Identifiants
pubmed: 33194666
doi: 10.3389/fonc.2020.571100
pmc: PMC7649363
doi:
Types de publication
Journal Article
Langues
eng
Pagination
571100Subventions
Organisme : NCI NIH HHS
ID : P01 CA100324
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA172637
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA237851
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216248
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA200561
Pays : United States
Organisme : NIH HHS
ID : S10 OD019961
Pays : United States
Informations de copyright
Copyright © 2020 Coste, Karagiannis, Wang, Xue, Lin, Skobe, Jones, Oktay, Condeelis and Entenberg.
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