Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer

被引:9
作者
Heublein, Sabine [1 ,2 ]
Page, Sabina [1 ]
Mayr, Doris [3 ]
Schmoeckel, Elisa [3 ]
Trillsch, Fabian [1 ]
Marme, Frederik [2 ]
Mahner, Sven [1 ]
Jeschke, Udo [1 ]
Vattai, Aurelia [1 ]
机构
[1] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Obstet & Gynecol, D-81377 Munich, Germany
[2] Heidelberg Univ, Dept Obstet & Gynecol, D-69117 Heidelberg, Germany
[3] Ludwig Maximilians Univ Munchen, Dept Pathol, D-81377 Munich, Germany
关键词
Gatipotuzumab; Tamoxifen; ovarian cancer; 4-Hydroxy-Tamoxifen (4-OHT); survival; BREAST-CANCER; TAMOXIFEN RESISTANCE; MUC1; PANKOMAB; ANTIBODY; REVEAL; MARKER;
D O I
10.3390/ijms20020295
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Anti-tumor efficacy of Gatipotuzumab, a therapeutic antibody targeting Tumor-Associated Mucin-1 (TA-MUC1), in relapsed ovarian cancer (OC) appeared to be rather heterogeneous. Whether adding a second anti-neoplastic drug may augment response towards Gatipotuzumab, has not been elucidated so far. Since it is known that anti-MUC1 antibodies may alter estrogen receptor activity in breast cancer, this potential interplay was investigated in OC. The correlation between TA-MUC1, estrogen receptors (ERs) and another 12 protein markers as well as their correlation with clinico-pathological parameters in 138 ovarian cancer cases was studied. Finally, Gatipotuzumab and 4-Hydroxy-TTamoxifen (4-OHT) as well as the combination of both was tested for its impact on cell viability in COV318, OV-90, OVCAR-3, and SKOV-3 cells. A strong positive correlation between TA-MUC1 and ERs was detected in OC tissue. Those cases missing ERs but staining positive for TA-MUC1 had significantly reduced overall survival. The combination of 4-OHT and Gatipotuzumab significantly reduced cell viability and was more effective than treatment with Gatipotuzumab alone. Co-stimulation with Gatipotuzumab enhanced the efficacy of 4-OHT in OVCAR-3 and SKOV-3. The data suggest an interplay of TA-MUC1 and ERs in OC. Whether the combination of Gatipotuzumab and TTamoxifen may enhance efficacy of either of the two drugs in vivo, or may even translate into a clinically relevant benefit over the respective monotherapies, remains to be investigated.
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页数:14
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