Paracellular and transcellular migration of metastatic cells through the cerebral endothelium
Open accessAbstract
Breast cancer and melanoma are among the most frequent cancer types leading to brain metastases. Despite the unquestionable clinical significance, important aspects of the development of secondary tumours of the central nervous system are largely uncharacterized, including extravasation of metastatic cells through the blood-brain barrier. By using transmission electron microscopy, here we followed interactions of cancer cells and brain endothelial cells during the adhesion, intercalation/incorporation and transendothelial migration steps. We observed that brain endothelial cells were actively involved in the initial phases of the extravasation by extending filopodia-like membrane protrusions towards the tumour cells. Melanoma cells tended to intercalate between endothelial cells and to transmigrate by utilizing the paracellular route. On the other hand, breast cancer cells were frequently incorporated into the endothelium and were able to migrate through the transcellular way from the apical to the basolateral side of brain endothelial cells. When co-culturing melanoma cells with cerebral endothelial cells, we observed N-cadherin enrichment at melanoma-melanoma and melanoma-endothelial cell borders. However, for breast cancer cells N-cadherin proved to be dispensable for the transendothelial migration both in vitro and in vivo. Our results indicate that breast cancer cells are more effective in the transcellular type of migration than melanoma cells.
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Lysis of naive PBMC during transmigration is an expected process.
“It seems that lysis of naive PBMC during transmigration is an expected process (Figure S13) (Bedoya et al., 1969; Herman et al., 2019).”
From Equid Herpesvirus-1 Exploits the Extracellular Matrix of Mononuclear Cells to Ensure Transport to Target Cells (2020) · cites this paper as Herman et al., 2019
The Discussion describes leukocyte transcellular migration but does not say that leukocytes lyse during it. The Results concern transmigrating melanoma cells, not naïve PBMC. Searches for PBMC lysis and cell death during transmigration found no passage addressing the claim. (LLM, conf=0.76)
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- Authors
- Herman, H., Fazakas, C., Haskó, J., Molnár, K., Mészáros, Á., Nyúl‐Tóth, Á., Szabó, G., Erdélyi, F., Ardelean, A., Hermenean, A., Krizbai, I. A., & Wilhelm, I.
- Affiliations
- Vasile Goldis Western University of Arad (RO)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- University of Szeged (HU)
- HUN-REN Institute of Experimental Medicine (HU)
- Corresponding author
- Hermenean, Anca
- Wilhelm, Imola
- ORCID
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2019-02-02
- Volume
- 23
- Issue
- 4
- Pages
- 2619-2631
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC6433661
- OpenAlex
- W2913325570
- Cited by
- 57
- References
- 35
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 12 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 1
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Funders
- Emberi Eroforrások Minisztériuma (UNKP‐18‐3‐1‐SZTE‐76, UNKP‐18‐4‐SZTE‐100)
- Magyar Tudományos Akadémia (BO/00334/16/8)
- Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (PN‐III‐P1‐1.1‐TE‐2016‐1352, PNCDI III—PCE 2016, PN‐III‐P4‐ID‐PCE‐2016‐0408, 188⁄2017)
- Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (K‐116158, GINOP‐2.3.2‐15‐2016‐00020, GINOP‐2.3.3‐15‐2016‐00030, GINOP‐2.3.2‐15‐2016‐00034)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- brain metastases, brain endothelium, transendothelial migration, transcellular migration, breast cancer, melanoma, blood-brain barrier, extravasation, N-cadherin, cell adhesion, filopodia, endothelial cell interaction
- MeSH terms
- Animals, Brain Neoplasms, Breast Neoplasms, Cell Movement, Cerebral Cortex, Endothelium, Vascular, Female, Humans, Melanocytes, Melanoma, Experimental, Mice, Inbred BALB C, Neoplasm Invasiveness, Neoplasm Transplantation, Organ Specificity, Skin Neoplasms, Tumor Cells, Cultured, Cadherins, Gene Expression, Coculture Techniques, Endothelial Cells, Cell Line, Tumor, Cell Proliferation, Mice, Primary Cell Culture
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