Transmigration characteristics of breast cancer and melanoma cells through the brain endothelium: Role of Rac and PI3K

Judit Molnár, Csilla Fazakas, János Haskó, Orsolya Sipos, Krisztina Nagy, Ádám Nyúl-Tóth, Attila E. Farkas, Attila G. Végh, György Váró, Péter Galajda, István A. Krizbai, Imola Wilhelm

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer.

Original languageEnglish
Pages (from-to)269-281
Number of pages13
JournalCell Adhesion and Migration
Volume10
Issue number3
DOIs
Publication statusPublished - May 3 2016

Keywords

  • Adhesion
  • Blood-brain barrier
  • Brain metastasis
  • Breast cancer
  • Cerebral endothelial cell
  • Melanoma
  • PI3K
  • Rac
  • Transmigration

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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