Phenotypic and functional differences between human liver cancer endothelial cells and liver sinusoidal endothelial cells.
OBJECTIVE
The phenotypic and functional characteristics of microvascular endothelial cells derived from human liver cancer (HLCEC) were analyzed in vitro and compared with those of human liver sinusoidal endothelial cells (LSEC).


RESULTS
Flow-cytometric and real-time PCR analysis indicated that expressions of tumor necrosis factor receptor (TNFR) p75, alphavbeta3 and alphavbeta5 were increased, while those of TNFR p55 and intercellular-adhesion molecule 1 (ICAM-1) were decreased in HLCEC compared with LSEC. The functional analysis indicated that HLCEC exhibited higher angiogenic ability than LSEC, including proliferation capacity, ability to form capillary-like networks and release of matrix metalloproteinases. In response to tumor necrosis factor, LSEC exhibited a significant dose-dependent cytotoxicity, while HLCEC did not. Moreover, the coagulant and fibrinolytic capacity was increased in HLCEC. In addition, tumor cell adherence was significantly higher on HLCEC than on LSEC, while leukocyte adherence was lower on HLCEC than on LSEC. The cytoadherence of HLCEC was inhibited by antibodies against alphavbeta3 and alphavbeta5,and of LSEC by antibodies against ICAM-1.


CONCLUSIONS
These results indicate that tumor-derived endothelial cells are phenotypically and functionally different from those derived from normal liver tissue. These differences are valuable for understanding tumor angiogenesis and metastasis.
Wu
Lian Qiu
LQ
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China.
Zhang
Wen Jian
WJ
Niu
Ji Xiao
JX
Ye
Li Ya
LY
Yang
Zhi Hua
ZH
Grau
Georges E
GE
Lou
Jin Ning
JN
D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008833:Microcirculation / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D039302:Integrin alphaVbeta3; D016023:Integrins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D047889:Receptors, Tumor Necrosis Factor, Type II; D019030:Receptors, Vitronectin; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; C064660:integrin alphaVbeta5; D018799:Intercellular Adhesion Molecule-1; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases