Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium.
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-1beta and TNF-alpha, but not with IL-6, resulted in at least 250% adhesion compared to control adhesion (p <or= 0.01). The effect of IL-1beta and TNF-alpha was concentration- and time-dependent. Comparable results were found for HUVECs. Tumor cell adhesion was not increased after preincubation of HT29 with TNF-alpha. 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-1beta and TNF-alpha 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.
ten Kate
Miranda
M
Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
Hofland
Leo J
LJ
van Grevenstein
Wilhelmina M U
WM
van Koetsveld
Peter V
PV
Jeekel
Johannes
J
van Eijck
Casper H J
CH
D002277:Carcinoma / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C052994:interleukin-1beta (163-171); D018799:Intercellular Adhesion Molecule-1