ArticleCancers2019
Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Tumor-Associated Macrophages (TAMs) in Cancer: Functional Programs, Metastatic Mechanisms, and Therapeutic Targeting.Cancers · 2026Review
- Forsythiaside A inhibits the progression of intrahepatic cholangiocarcinoma partially via suppressing oxidative stress-induced hepatic stellate cell activation and macrophage polarization.BMC biotechnology · 2026Article
- Single cell mapping of B and T cell dynamics in breast cancer lymph node metastasis.Frontiers in bioinformatics · 2026Article
- Modelling the metastatic immune microenvironment in triple-negative breast cancer.Breast cancer research : BCR · 2025Article
- Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.Oncogene · 2025Article
- Review
- Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.The Journal of clinical investigation · 2025Review
- Review
- Intravital Imaging of Immune Responses in the Cancer Microenvironment.Cancer medicine · 2025Review
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Signaling events at TMEM doorways provide potential targets for inhibiting breast cancer dissemination.bioRxiv : the preprint server for biology · 2024Article
- Breast cancer brain metastasis: from etiology to state-of-the-art modeling.Journal of biological engineering · 2023Review
- Intravital imaging to study cancer progression and metastasis.Nature reviews. Cancer · 2023Review
- Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy.NPJ breast cancer · 2022Article
- The gate to metastasis: key players in cancer cell intravasation.The FEBS journal · 2022Review
- A nomogram for survival prediction in 275,812 U.S. patients with breast cancer: a population-based cohort study based on the SEER database.Gland surgery · 2022Article
- NAD(P)H fluorescence lifetime imaging of live intestinal nematodes reveals metabolic crosstalk between parasite and host.Scientific reports · 2022Article
- An Immunological Perspective of Circulating Tumor Cells as Diagnostic Biomarkers and Therapeutic Targets.Life (Basel, Switzerland) · 2022Review
- Article
- Application of Microfluidic Systems for Breast Cancer Research.Micromachines · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.