Tumor necrosis factor-α stimulates attachment of small cell lung carcinoma to endothelial cells

F. D. Sheski, V. Natarajan, Scott T. Pottratz

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Tumor cell attachment to endothelial cells (ECs) is an important step in the metastasis of small cell lung carcinoma (SCLC). Tumor necrosis factor-α (TNF-α) stimulation of ECs increases the attachment of some malignant cell types to ECs by affecting the expression of cell adhesion molecules (CAMs). Similarly, the inhibition of EC protein kinase C (PKC) and tyrosine kinase (TK) pathways modulates TNF-α-mediated effects on CAM expression. We hypothesized that TNF-α would increase SCLC attachment to ECs by affecting CAM expression through activation of PKC and TK pathways. To test this hypothesis, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (0 to 500 U/mL) for variable time periods (1 to 24 hours), and the attachment of H82 cells (an SCLC cell line) to the HUVECs was quantified. TNF-α stimulation of the HUVECs increased H82 attachment from 28.1% ± 1.6% to 48.8% ± 1.7% (P < .05). Preincubation of HUVECs with the PKC inhibitors bis-indolylmaleimide (BIN) or calphostin C or the TK inhibitors genistein or herbimycin A (HMA) blocked the TNF-α-induced increase in H82 cell attachment. The addition of antibodies to vitronectin (Vn) or β1-integrin to TNF-α-activated HUVECs before the addition of the H82 cells also significantly decreased H82 attachment, whereas the addition of antibodies to E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), neural cell adhesion molecule (NCAM), sialyl-Lewis(x), fibronectin (Fn), α(v)-integrin, α3-integrin, α4-integrin, or α5-integrin had no effect on SCLC attachment. In summary, the TNF-α-mediated increase in SCLC attachment to ECs appears to be mediated by the activation of EC PKC and TK pathways as well as through effects on the function or expression of EC Vn and β1 integrin.

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalJournal of Laboratory and Clinical Medicine
Volume133
Issue number3
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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