Paracellular and transcellular migration of metastatic cells through the cerebral endothelium

Hildegard Herman, Csilla Fazakas, János Haskó, Kinga Molnár, Ádám Mészáros, Ádám Nyúl-Tóth, Gábor Szabó, F. Erdélyi, Aurel Ardelean, Anca Hermenean, I. Krizbai, I. Wilhelm

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2619-2631
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

Transcellular Cell Migration
Endothelium
Melanoma
Endothelial Cells
Breast Neoplasms
Transendothelial and Transepithelial Migration
Cadherins
Brain
Central Nervous System Neoplasms
Pseudopodia
Blood-Brain Barrier
Transmission Electron Microscopy
Cell Adhesion
Brain Neoplasms
Cell Communication
Neoplasms

Keywords

  • blood-brain barrier
  • brain metastasis
  • breast cancer
  • cerebral endothelial cell
  • incorporation
  • intercalation
  • melanoma
  • N-cadherin
  • paracellular
  • transcellular

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Paracellular and transcellular migration of metastatic cells through the cerebral endothelium. / Herman, Hildegard; Fazakas, Csilla; Haskó, János; Molnár, Kinga; Mészáros, Ádám; Nyúl-Tóth, Ádám; Szabó, Gábor; Erdélyi, F.; Ardelean, Aurel; Hermenean, Anca; Krizbai, I.; Wilhelm, I.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 4, 01.04.2019, p. 2619-2631.

Research output: Contribution to journalArticle

Herman, H, Fazakas, C, Haskó, J, Molnár, K, Mészáros, Á, Nyúl-Tóth, Á, Szabó, G, Erdélyi, F, Ardelean, A, Hermenean, A, Krizbai, I & Wilhelm, I 2019, 'Paracellular and transcellular migration of metastatic cells through the cerebral endothelium', Journal of Cellular and Molecular Medicine, vol. 23, no. 4, pp. 2619-2631. https://doi.org/10.1111/jcmm.14156
Herman, Hildegard ; Fazakas, Csilla ; Haskó, János ; Molnár, Kinga ; Mészáros, Ádám ; Nyúl-Tóth, Ádám ; Szabó, Gábor ; Erdélyi, F. ; Ardelean, Aurel ; Hermenean, Anca ; Krizbai, I. ; Wilhelm, I. / Paracellular and transcellular migration of metastatic cells through the cerebral endothelium. In: Journal of Cellular and Molecular Medicine. 2019 ; Vol. 23, No. 4. pp. 2619-2631.
@article{09cc913158a8410fb936ec64dfcad81f,
title = "Paracellular and transcellular migration of metastatic cells through the cerebral endothelium",
abstract = "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.",
keywords = "blood-brain barrier, brain metastasis, breast cancer, cerebral endothelial cell, incorporation, intercalation, melanoma, N-cadherin, paracellular, transcellular",
author = "Hildegard Herman and Csilla Fazakas and J{\'a}nos Hask{\'o} and Kinga Moln{\'a}r and {\'A}d{\'a}m M{\'e}sz{\'a}ros and {\'A}d{\'a}m Ny{\'u}l-T{\'o}th and G{\'a}bor Szab{\'o} and F. Erd{\'e}lyi and Aurel Ardelean and Anca Hermenean and I. Krizbai and I. Wilhelm",
year = "2019",
month = "4",
day = "1",
doi = "10.1111/jcmm.14156",
language = "English",
volume = "23",
pages = "2619--2631",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Paracellular and transcellular migration of metastatic cells through the cerebral endothelium

AU - Herman, Hildegard

AU - Fazakas, Csilla

AU - Haskó, János

AU - Molnár, Kinga

AU - Mészáros, Ádám

AU - Nyúl-Tóth, Ádám

AU - Szabó, Gábor

AU - Erdélyi, F.

AU - Ardelean, Aurel

AU - Hermenean, Anca

AU - Krizbai, I.

AU - Wilhelm, I.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - blood-brain barrier

KW - brain metastasis

KW - breast cancer

KW - cerebral endothelial cell

KW - incorporation

KW - intercalation

KW - melanoma

KW - N-cadherin

KW - paracellular

KW - transcellular

UR - http://www.scopus.com/inward/record.url?scp=85063412914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063412914&partnerID=8YFLogxK

U2 - 10.1111/jcmm.14156

DO - 10.1111/jcmm.14156

M3 - Article

VL - 23

SP - 2619

EP - 2631

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 4

ER -