[Effects of human peritoneal mesothelial cells on angiogenesis factor expression and secretion of ovarian carcinoma cells].
OBJECTIVE
To investigate the impact of human peritoneal mesothelial cells (HPMC) on angiogenesis factor expression and secretion of ovarian carcinoma cell line SKOV3.


METHODS
The conditioned medium with HPMC was tested by ELISA for tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-1beta). Millicell was used to co-culture HPMC and ovarian carcinoma cell line SKOV3 in the presence or absence of neutralizing antibody against TNF-alpha or IL-1beta. RT-PCR was used to detect vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene expression in SKOV3 cells. VEGF and bFGF protein levels in the SKOV3 conditioned medium were assessed by ELISA.


RESULTS
Conditioned medium with HPMC contained both TNF-alpha and IL-1beta. SKOV3 co-cultured with HPMC expressed higher levels of VEGF and bFGF mRNA and secreted at increased levels of both VEGF and bFGF, in comparison with those in SKOV3 cells cultured alone (P < 0.01). Addition of neutralizing antibody against TNF-alpha or IL-1beta during co-cultures resulted in decrease in mRNA expression and secretion of VEGF and bFGF in SKOV3 cells. When both antibodies were administered during co-culture, additive decrease was observed.


CONCLUSIONS
HPMC can act in a paracrine fashion to stimulate ovarian tumor cells to produce and secret at increased levels of VEGF and bFGF through TNF-alpha and IL-1beta, and contribute to angiogenesis and peritoneal metastasis of ovarian cancer.
Zhang
Jing-Jing
JJ
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China.
Wang
Bo
B
Liu
Zeng-Juan
ZJ
D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D000906:Antibodies; D017077:Culture Media, Conditioned; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2