Mechanism of increased binding of small cell lung cancer to TNF-α stimulated endothelium

Francis D. Sheski, V. Natarajan, S. T. Pottratz

Research output: Contribution to journalArticle

Abstract

Purpose: Binding of cancer cells to the endothelium is an early step in the metastasis of small cell lung cancer (SCLC). Our past work has shown that TNF stimulation of endothelial cells (EC) increases H82 cell (SCLC line) binding. We hypothesize that increased binding results from changes in EC adhesion molecule expression and that these changes may be mediated by protein kinase C (PKC) or tyrosine kinase (TK) activation. Methode: Binding of 51Cr-labeled H82 cells to TNF stimulated EC was quantified using a standard assay. To assess the role of EC adhesion molecules in H82 binding, neutralizing antibodies to E-selectin, P-selectin, ICAM-1, VCAM or siaryl Lewis X were utilized. To determine the role of activation of EC PKC and TK in H82 attachment, either PKC or TK inhibitors were added to the EC prior to TNF-α stimulation. Results: Increased attachment of H82 cells to TNF-stimulated EC (control, 28.8 ± 3% vs. TNF, 43.4 ± 4%, p < 0.05) was blocked by antibody to E-selectin, but not by antibodies to the other adhesion molecules. Pretreatment of the EC with either of the PKC inhibitors, BIN (10μM) and calphostin C (5μM), or either of the TK inhibitors, genistein (60μM) and erbstatin analog (10μM), blocked the TNF-mediated increase in H82 attachment. Conclusions: TNF-α stimulation of EC increases SCLC attachment via E-selectin and activation of PKC and TK pathways. Clinical Implications: TNF-α may be an important factor in the metastasis of SCLC through regulation of EC adhesion molecule expression.

Original languageEnglish (US)
Pages (from-to)157S
JournalChest
Volume110
Issue number4 SUPPL.
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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