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LUNG TUMOUR SECRETED VEGF AND TNF-α INDUCE EXPRESSION OF ADHESION MOLECULES ON CEREBRAL ENDOTHELIAL CELLS
  1. N Gutowski1,2,*,
  2. S Rai1,2,
  3. JL Whatmore1,2
  1. 1Peninsula Medical School
  2. 2Royal Devon and Exeter Hospital

    Abstract

    Introduction Lung tumours frequently metastasise to the brain; this involves specific adhesive interactions between tumour cells and cerebral endothelial cells. Vascular endothelial growth factor (VEGF) and tumour necrosis factor- α (TNF-α) are released by two non-small cell lung cancer (NSCLC) cell lines—A549 and SKMES-1. The effects of these factors on human cerebral microvascular endothelial cell (hCMEC) adhesion molecule expression have been studied.

    Methods Adhesion molecule expression: Surface expression of E-selectin, inter-cellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) on hCMECs were analysed by an ELISA. hCMECs were starved overnight and treated for 4 h (E-selectin) and 24 h (ICAM-1 and VCAM-1) with 0.2, 10 and 20 ng/ml of VEGF and 100, 500 and 2500 pg/ml of TNF-α; expression of adhesion molecules was measured by ELISA.

    Adhesion under flow: A549 and SKMES-1 cells were flowed over VEGF (0.2 ng/ml) and TNF- α (100 pg/ml) treated hCMECs, adherent cells were counted.

    Results Both VEGF and TNF- α significantly increased E-selectin, ICAM-1 and VCAM-1 expression. Flow adhesion assays showed VEGF and TNF-α increased adherence of lung tumour cells to the hCMEC monolayer.

    Conclusion Factors released from lung tumour cells such as VEGF and TNF-α increase expression of endothelial adhesion molecules and may enhance tumour cell adhesion to cerebral endothelial cells.

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