Abstract 5166: THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA

Ovarian carcinoma is the most lethal gynecological cancer and currently ranks as the fifth in causing cancer-related deaths among women. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progre...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.5166-5166
Main Authors: chehover, michal, Tropé, Claes, Reich, Reuven, Davidson, Ben
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Tropé, Claes
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Davidson, Ben
description Ovarian carcinoma is the most lethal gynecological cancer and currently ranks as the fifth in causing cancer-related deaths among women. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Three WNT signaling pathways have been characterized: the canonical WNT pathway, the non-canonical planar cell polarity pathway, and the non-canonical WNT/calcium pathway. All three WNT signaling pathways are activated by the binding of a WNT-protein ligand to a Frizzled family receptor, which passes the biological signal inside the cell. Several lines of research indicate on the involvement of these pathways also in ovarian carcinomas. However, the specific pathway or their regulation in the process of tumor progression in this disease has not been elucidated, so far. The aim of the current study is to identify the acting components of these pathways during tumor progression namely, which receptors and which ligands are activated at the different stages of ovarian carcinoma. We have analyzed the expression 7 frizzle genes (fzd1, 2, 4, 5, 6, 7, 8, 10), 4 WNT genes (wnt 2,3,4,5a,7) and 2 co-receptors LRP (5,6) on 222 samples (143 effusions, 44 primary, and 35 metastatic lesions) using real-time PCR. All the tested genes were found to be expressed at all sites. FRZ5 (p = 0.002), FRZ6 (p
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This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Three WNT signaling pathways have been characterized: the canonical WNT pathway, the non-canonical planar cell polarity pathway, and the non-canonical WNT/calcium pathway. All three WNT signaling pathways are activated by the binding of a WNT-protein ligand to a Frizzled family receptor, which passes the biological signal inside the cell. Several lines of research indicate on the involvement of these pathways also in ovarian carcinomas. However, the specific pathway or their regulation in the process of tumor progression in this disease has not been elucidated, so far. The aim of the current study is to identify the acting components of these pathways during tumor progression namely, which receptors and which ligands are activated at the different stages of ovarian carcinoma. We have analyzed the expression 7 frizzle genes (fzd1, 2, 4, 5, 6, 7, 8, 10), 4 WNT genes (wnt 2,3,4,5a,7) and 2 co-receptors LRP (5,6) on 222 samples (143 effusions, 44 primary, and 35 metastatic lesions) using real-time PCR. All the tested genes were found to be expressed at all sites. FRZ5 (p = 0.002), FRZ6 (p&lt;0.001), Wnt2 (p = 0.029), Wnt3 (p = 0.034) and Wnt6 (p = 0.022) were lower in effusion-derived cells compared to solids lesions. Further, Wnt2 expression was higher in pre-chemo (p = 0.037) samples compared to post-chemo ones. FRZ6 expression was higher in FIGO stage IV compared to stage III of the disease (p = 0.041), and FRZ4 expression was higher in cases with lower residual disease volume (p = 0.002). Wnt5a was higher in patients with better (complete) response (p = 0.019). FRZ6 expression was associated with poor overall survival (p = 0.045) and progression-free survival (p = 0.009). FRZ10 expression was associated with better overall survival (p = 0.005) and progression-free survival (p = 0.005). Citation Format: michal chehover, Claes Tropé, Reuven Reich, Ben Davidson. THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. 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This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Three WNT signaling pathways have been characterized: the canonical WNT pathway, the non-canonical planar cell polarity pathway, and the non-canonical WNT/calcium pathway. All three WNT signaling pathways are activated by the binding of a WNT-protein ligand to a Frizzled family receptor, which passes the biological signal inside the cell. Several lines of research indicate on the involvement of these pathways also in ovarian carcinomas. However, the specific pathway or their regulation in the process of tumor progression in this disease has not been elucidated, so far. The aim of the current study is to identify the acting components of these pathways during tumor progression namely, which receptors and which ligands are activated at the different stages of ovarian carcinoma. We have analyzed the expression 7 frizzle genes (fzd1, 2, 4, 5, 6, 7, 8, 10), 4 WNT genes (wnt 2,3,4,5a,7) and 2 co-receptors LRP (5,6) on 222 samples (143 effusions, 44 primary, and 35 metastatic lesions) using real-time PCR. All the tested genes were found to be expressed at all sites. FRZ5 (p = 0.002), FRZ6 (p&lt;0.001), Wnt2 (p = 0.029), Wnt3 (p = 0.034) and Wnt6 (p = 0.022) were lower in effusion-derived cells compared to solids lesions. Further, Wnt2 expression was higher in pre-chemo (p = 0.037) samples compared to post-chemo ones. FRZ6 expression was higher in FIGO stage IV compared to stage III of the disease (p = 0.041), and FRZ4 expression was higher in cases with lower residual disease volume (p = 0.002). Wnt5a was higher in patients with better (complete) response (p = 0.019). FRZ6 expression was associated with poor overall survival (p = 0.045) and progression-free survival (p = 0.009). FRZ10 expression was associated with better overall survival (p = 0.005) and progression-free survival (p = 0.005). Citation Format: michal chehover, Claes Tropé, Reuven Reich, Ben Davidson. THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. 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This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Three WNT signaling pathways have been characterized: the canonical WNT pathway, the non-canonical planar cell polarity pathway, and the non-canonical WNT/calcium pathway. All three WNT signaling pathways are activated by the binding of a WNT-protein ligand to a Frizzled family receptor, which passes the biological signal inside the cell. Several lines of research indicate on the involvement of these pathways also in ovarian carcinomas. However, the specific pathway or their regulation in the process of tumor progression in this disease has not been elucidated, so far. The aim of the current study is to identify the acting components of these pathways during tumor progression namely, which receptors and which ligands are activated at the different stages of ovarian carcinoma. We have analyzed the expression 7 frizzle genes (fzd1, 2, 4, 5, 6, 7, 8, 10), 4 WNT genes (wnt 2,3,4,5a,7) and 2 co-receptors LRP (5,6) on 222 samples (143 effusions, 44 primary, and 35 metastatic lesions) using real-time PCR. All the tested genes were found to be expressed at all sites. FRZ5 (p = 0.002), FRZ6 (p&lt;0.001), Wnt2 (p = 0.029), Wnt3 (p = 0.034) and Wnt6 (p = 0.022) were lower in effusion-derived cells compared to solids lesions. Further, Wnt2 expression was higher in pre-chemo (p = 0.037) samples compared to post-chemo ones. FRZ6 expression was higher in FIGO stage IV compared to stage III of the disease (p = 0.041), and FRZ4 expression was higher in cases with lower residual disease volume (p = 0.002). Wnt5a was higher in patients with better (complete) response (p = 0.019). FRZ6 expression was associated with poor overall survival (p = 0.045) and progression-free survival (p = 0.009). FRZ10 expression was associated with better overall survival (p = 0.005) and progression-free survival (p = 0.005). Citation Format: michal chehover, Claes Tropé, Reuven Reich, Ben Davidson. THE WNT SIGNALING PATHWAY IN THE OVARIAN CARCINOMA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5166. doi:10.1158/1538-7445.AM2015-5166</abstract><doi>10.1158/1538-7445.AM2015-5166</doi></addata></record>
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