Cancer cell-derived IL-1alpha induces IL-8 release in endothelial cells.
OBJECTIVE
Cancer cells release a multitude of cytokines and growth factors that influence neighboring cells and help establish a favorable environment for tumor development. As part of our studies designed to elucidate the complex cellular interactions within the tumor microenvironment that facilitate tumor development, we investigated cancer cell-induced changes in gene expression in endothelial cells.


METHODS
After treatment of human umbilical vein endothelial cells (HUVEC) with conditioned medium (CM) of SNUC5 colon cancer cells, gene expression profile in HUVEC was analyzed using cDNA microarray. Neutralizing antibodies against pro-inflammatory cytokines were used to identify the major effecter in SNUC5 CM.


RESULTS
IL-8 was one of the four genes up-regulated over fourfold, and IL-1alpha in SNUC5 CM was revealed as a major effecter of IL-8 over-expression and release, which was nearly completely neutralized by anti-IL-1alpha antibody. Constitutive secretion of IL-1alpha was confirmed in many other human cancer cells.


CONCLUSIONS
IL-1alpha is constitutively expressed in many human cancer cells and directly induces IL-8 secretion in neighboring endothelial cells.
Rhim
Jung-Hyo
JH
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Kim
Sin-Ae
SA
Lee
Ji-Eun
JE
Kim
Dong-Jo
DJ
Chung
Hong Keun
HK
Shin
Kum-Joo
KJ
Chung
Junho
J
D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D053582:Interleukin-1alpha; D016209:Interleukin-8; D012333:RNA, Messenger