TY - JOUR
T1 - Expression of CD40 and growth-inhibitory activity of CD40 ligand in ovarian cancer cell lines
AU - Melichar, Bohuslav
AU - Patenia, Rebecca
AU - Gallardo, Stacie
AU - Melicharová, Karolina
AU - Hu, Wei
AU - Freedman, Ralph S.
PY - 2007/3
Y1 - 2007/3
N2 - Objective: Soluble recombinant human CD40 ligand trimer (rhuCD40Lt) has shown antitumor activity in preclinical and clinical studies. We evaluated the effect of rhuCD40Lt on epithelial ovarian carcinoma (EOC) cell lines. Methods: Expression of the receptor, CD40, was determined by reverse transcriptase-polymerase chain reaction and flow cytometry, and antiproliferative effects of rhuCD40Lt, either alone or in combination with recombinant interferon-γ (rIFN-γ), were examined in 8 EOC lines. Results: Expression of CD40 was elevated in 5 out of 8 EOC cell lines examined by flow cytometry, and the presence of CD40 transcripts was detected by RT-PCR in all 8 cell lines. CD40 expression was increased by rIFN-γ, but treatment with rhuCD40Lt decreased CD40 expression in 4 of the 5 lines that had shown elevated CD40 expression. rhuCD40Lt had a growth-inhibitory effect on 2774 cells, which also exhibited the highest level of CD40 expression. Growth-inhibitory effect of rhuCD40Lt was additive with rIFN-γ on 2774, NMP-1, a cisplatin-resistant subline of OVCAR3, and HEY cell lines. The number of apoptotic tumor cells was increased following treatment with rhuCD40Lt. Conclusions: CD40 is expressed on EOC cell lines, and expression was found at the transcript level in all of the EOC lines examined. rIFN-γ enhances CD40 expression, though a decrease in CD40 expression was observed following treatment with rhuCD40Lt. Growth-inhibitory activity of rhuCD40Lt on EOC lines that express CD40 could be enhanced when rhuCD40Lt treatment was combined with rIFN-γ. These results suggest that future studies of the combination of rhuCD40Lt and rIFN-γ might warrant consideration.
AB - Objective: Soluble recombinant human CD40 ligand trimer (rhuCD40Lt) has shown antitumor activity in preclinical and clinical studies. We evaluated the effect of rhuCD40Lt on epithelial ovarian carcinoma (EOC) cell lines. Methods: Expression of the receptor, CD40, was determined by reverse transcriptase-polymerase chain reaction and flow cytometry, and antiproliferative effects of rhuCD40Lt, either alone or in combination with recombinant interferon-γ (rIFN-γ), were examined in 8 EOC lines. Results: Expression of CD40 was elevated in 5 out of 8 EOC cell lines examined by flow cytometry, and the presence of CD40 transcripts was detected by RT-PCR in all 8 cell lines. CD40 expression was increased by rIFN-γ, but treatment with rhuCD40Lt decreased CD40 expression in 4 of the 5 lines that had shown elevated CD40 expression. rhuCD40Lt had a growth-inhibitory effect on 2774 cells, which also exhibited the highest level of CD40 expression. Growth-inhibitory effect of rhuCD40Lt was additive with rIFN-γ on 2774, NMP-1, a cisplatin-resistant subline of OVCAR3, and HEY cell lines. The number of apoptotic tumor cells was increased following treatment with rhuCD40Lt. Conclusions: CD40 is expressed on EOC cell lines, and expression was found at the transcript level in all of the EOC lines examined. rIFN-γ enhances CD40 expression, though a decrease in CD40 expression was observed following treatment with rhuCD40Lt. Growth-inhibitory activity of rhuCD40Lt on EOC lines that express CD40 could be enhanced when rhuCD40Lt treatment was combined with rIFN-γ. These results suggest that future studies of the combination of rhuCD40Lt and rIFN-γ might warrant consideration.
KW - Ovarian cancer
KW - cD40
KW - cD40 ligand
UR - http://www.scopus.com/inward/record.url?scp=33846916705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846916705&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2006.10.056
DO - 10.1016/j.ygyno.2006.10.056
M3 - Article
C2 - 17166566
AN - SCOPUS:33846916705
SN - 0090-8258
VL - 104
SP - 707
EP - 713
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -