Purpose: Small cell lung carcinoma (SCLC) is characterized by early metastasis. Attachment of cancer cells to the vascular endothelium is a critical event in the development of metastatic disease. Tumor necrosis factor-α (TNF) is a cytokine known to increase expression of endothelial cell (EC) adhesion molecules. Previous studies have shown that intracellular signalling by TNF may involve generation of reactive oxygen species. Therefore, we hypothesized that TNF would increase attachment of SCLC cells to EC and that anti-oxidants such as α-tocopherol and pyrollidine dithiocarbamate (PDTC) would block the TNF-mediated activation of EC, resulting in decreased cancer cell attachment. Methods: Attachment of 51Cr-labeled H82 cells (an SCLC cell line) to human umbilical vein EC was quantified using a standard attachment assay. Results: TNF activation of EC resulted in a time and concentration dependent increase in H82 cell attachment, with maximal attachment occurring after addition of 50 U/ml of TNF for 4 hours. Attachment increased from 10.2 ± 2.5% (control) to 24.4 ± 3.6% (TNF 50 U/ml × 4 hrs). Pre-incubation of the EC with α-tocopherol (50 μM) or PDTC (100 μM) completely inhibited the TNF-mediated increase in H82 cell attachment, but did not effect H82 cell attachment to untreated EC. Conclusions: These data demonstrate that the anti-oxidants α-tocopherol and PDTC block TNF-mediated increases in cancer cell attachment to EC. Clinical Implications: Anti-oxidants may be an important factor in the development of metastatic SCLC through their effects on cancer cell adhesion to the endothelium.
|Original language||English (US)|
|Issue number||4 SUPPL.|
|State||Published - Oct 1 1996|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine