Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium

✍ Scribed by Miranda Ten Kate; Leo J. Hofland; Wilhelmina M.U. van Grevenstein; Peter V. van Koetsveld; Johannes Jeekel; Casper H.J. van Eijck

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: French
• Weight: 143 KB
• Volume: 112
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.20506

✦ Synopsis

Abstract

In this experimental study, the influence of surgery‐induced proinflammatory cytokines on tumor recurrence in the lung was investigated. A reproducible human in vitro assay was developed to study the adhesion of HT29 colon carcinoma cells to monolayers of microvascular endothelial cells of the lung (HMVECs‐L) or human umbilical venous endothelial cells (HUVECs). Preincubation of HMVECs‐L with maximally active concentrations of IL‐1β and TNF‐α, but not with IL‐6, resulted in at least 250% adhesion compared to control adhesion (p ≤ 0.01). The effect of IL‐1β and TNF‐α was concentration‐ and time‐dependent. Comparable results were found for HUVECs. Tumor cell adhesion was not increased after preincubation of HT29 with TNF‐α. Enzyme immunoassays of cytokine‐preincubated HUVECs and HMVECs‐L showed concentration‐ and time‐dependent upregulation of E‐selectin, ICAM‐1 and VCAM‐1 expression. In addition, LFA‐1 and VLA‐4 were only expressed on HMVECs‐L, creating more binding possibilities for HMVECs‐L compared to HUVECs. Inhibition assays with anti‐E‐selectin monoclonal antibody significantly decreased tumor cell adhesion to HUVECs; however, it did not affect tumor cell adhesion to HMVECs‐L. Furthermore, anti‐ICAM‐1 and anti‐VCAM‐1 antibodies did not affect adhesion. Our results prove IL‐1β and TNF‐α promote tumor cell adhesion to HMVECs‐L in vitro and may therefore account for enhanced tumor recurrence in the lung seen after major surgical trauma. The adhesion of HT29 to HUVEC is inhibitable by E‐selectin antibodies, whereas the adhesion to HMVEC‐L is not inhibitable by these antibodies. Probably not one but a complex of adhesion molecules is responsible for enhanced adhesion to HMVECs‐L. © 2004 Wiley‐Liss, Inc.