Anti-oxidants inhibit the attachment of small cell lung carcinoma to TNF-activated endothelial cells

Scott T. Pottratz, Francis Sheski, D. M. Bernardo, V. Natarajan

Research output: Contribution to journalArticle

Abstract

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 languageEnglish
JournalChest
Volume110
Issue number4 SUPPL.
StatePublished - Oct 1996

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Small Cell Lung Carcinoma
Oxidants
Endothelial Cells
Tumor Necrosis Factor-alpha
Tocopherols
Neoplasms
Human Umbilical Vein Endothelial Cells
Vascular Endothelium
Cell Adhesion Molecules
Cell Adhesion
Endothelium
Reactive Oxygen Species
Cytokines
Neoplasm Metastasis
Cell Line

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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Anti-oxidants inhibit the attachment of small cell lung carcinoma to TNF-activated endothelial cells. / Pottratz, Scott T.; Sheski, Francis; Bernardo, D. M.; Natarajan, V.

In: Chest, Vol. 110, No. 4 SUPPL., 10.1996.

Research output: Contribution to journalArticle

Pottratz, Scott T. ; Sheski, Francis ; Bernardo, D. M. ; Natarajan, V. / Anti-oxidants inhibit the attachment of small cell lung carcinoma to TNF-activated endothelial cells. In: Chest. 1996 ; Vol. 110, No. 4 SUPPL.
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abstract = "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.",
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