Transmigration of breast cancer and melanoma cells through the blood-brain barrier: similarities and differences

Molnár Judit
Transmigration of breast cancer and melanoma cells through the blood-brain barrier: similarities and differences.
Doctoral thesis (PhD), University of Szeged.
(2016) (Unpublished)

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Abstract in foreign language

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.

Item Type: Thesis (Doctoral thesis (PhD))
Creators: Molnár Judit
Hungarian title: Az emlőkarcinóma és melanóma sejtek átvándorlása a vér-agy gáton keresztül: hasonlóságok és különbségek
Supervisor(s):
Supervisor
Position, academic title, institution
MTMT author ID
Krizbai István
tudományos tanácsadó, MTA SZBK Biofizikai Intézet
10008997
Wilhelm Imola
tudományos munkatárs, MTA SZBK Biofizikai Intézet
10013652
Subjects: 03. Medical and health sciences > 03.01. Basic medicine
Divisions: Doctoral School of Theoretical Medicine
Discipline: Medicine > Theoretical Medicine
Language: English
Date: 2016. May 17.
Item ID: 2967
MTMT identifier of the thesis: 3105146
doi: https://doi.org/10.14232/phd.2967
Date Deposited: 2016. May. 06. 15:14
Last Modified: 2020. May. 04. 12:55
Depository no.: B 6045
URI: https://doktori.bibl.u-szeged.hu/id/eprint/2967
Defence/Citable status: Defended.

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