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.
