Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance
Ovarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/958 |
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| author | Deepak Parashar Anjali Geethadevi Sonam Mittal Lindsey A. McAlarnen Jasmine George Ishaque P. Kadamberi Prachi Gupta Denise S. Uyar Elizabeth E. Hopp Holli Drendel Erin A. Bishop William H. Bradley Kathleen M. Bone Janet S. Rader Sunila Pradeep Pradeep Chaluvally-Raghavan |
| author_facet | Deepak Parashar Anjali Geethadevi Sonam Mittal Lindsey A. McAlarnen Jasmine George Ishaque P. Kadamberi Prachi Gupta Denise S. Uyar Elizabeth E. Hopp Holli Drendel Erin A. Bishop William H. Bradley Kathleen M. Bone Janet S. Rader Sunila Pradeep Pradeep Chaluvally-Raghavan |
| author_sort | Deepak Parashar |
| collection | DOAJ |
| description | Ovarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant to apoptosis and chemotherapeutic agents. However, the precise mechanism as an oncogenic addiction that makes 3D spheroids resistant to apoptosis and chemotherapeutic agents is not understood. To study the signaling addiction mechanism that occurs during cancer progression in patients, we developed an endometrioid subtype ovarian cancer cell line named ‘MCW-OV-SL-3’ from the ovary of a 70-year-old patient with stage 1A endometrioid adenocarcinoma of the ovary. We found that the cell line MCW-OV-SL-3 exhibits interstitial duplication of 1q (q21–q42), where this duplication resulted in high expression of the PIK3C2B gene and aberrant activation of PI3K-AKT-ERK signaling. Using short tandem repeat (STR) analysis, we demonstrated that the cell line exhibits a unique genetic identity compared to existing ovarian cancer cell lines. Notably, the MCW-OV-SL-3 cell line was able to form 3D spheroids spontaneously, which is an inherent property of tumor cells when plated on cell culture dishes. Importantly, the tumor spheroids derived from the MCW-OV-SL-3 cell line expressed high levels of c-Kit, PROM1, ZEB1, SNAI, VIM, and Twist1 compared to 2D monolayer cells. We also observed that the hyperactivation of ERK and PI3K/AKT signaling in these cancer cells resulted in resistance to cisplatin. In summary, the MCW-OV-SL3 endometrioid cell line is an excellent model to study the mechanism of cancer stemness and chemoresistance in endometrioid ovarian cancer. |
| first_indexed | 2024-03-09T22:24:20Z |
| format | Article |
| id | doaj.art-a97aba7519e242948429d66cdead4250 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:24:20Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a97aba7519e242948429d66cdead42502023-11-23T19:09:10ZengMDPI AGCancers2072-66942022-02-0114495810.3390/cancers14040958Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and ChemoresistanceDeepak Parashar0Anjali Geethadevi1Sonam Mittal2Lindsey A. McAlarnen3Jasmine George4Ishaque P. Kadamberi5Prachi Gupta6Denise S. Uyar7Elizabeth E. Hopp8Holli Drendel9Erin A. Bishop10William H. Bradley11Kathleen M. Bone12Janet S. Rader13Sunila Pradeep14Pradeep Chaluvally-Raghavan15Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USADepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USAOvarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant to apoptosis and chemotherapeutic agents. However, the precise mechanism as an oncogenic addiction that makes 3D spheroids resistant to apoptosis and chemotherapeutic agents is not understood. To study the signaling addiction mechanism that occurs during cancer progression in patients, we developed an endometrioid subtype ovarian cancer cell line named ‘MCW-OV-SL-3’ from the ovary of a 70-year-old patient with stage 1A endometrioid adenocarcinoma of the ovary. We found that the cell line MCW-OV-SL-3 exhibits interstitial duplication of 1q (q21–q42), where this duplication resulted in high expression of the PIK3C2B gene and aberrant activation of PI3K-AKT-ERK signaling. Using short tandem repeat (STR) analysis, we demonstrated that the cell line exhibits a unique genetic identity compared to existing ovarian cancer cell lines. Notably, the MCW-OV-SL-3 cell line was able to form 3D spheroids spontaneously, which is an inherent property of tumor cells when plated on cell culture dishes. Importantly, the tumor spheroids derived from the MCW-OV-SL-3 cell line expressed high levels of c-Kit, PROM1, ZEB1, SNAI, VIM, and Twist1 compared to 2D monolayer cells. We also observed that the hyperactivation of ERK and PI3K/AKT signaling in these cancer cells resulted in resistance to cisplatin. In summary, the MCW-OV-SL3 endometrioid cell line is an excellent model to study the mechanism of cancer stemness and chemoresistance in endometrioid ovarian cancer.https://www.mdpi.com/2072-6694/14/4/958epithelial ovarian cancercancer stemnessspheroidsPI3K/AKT signalingsignaling addictioncancer cell line development |
| spellingShingle | Deepak Parashar Anjali Geethadevi Sonam Mittal Lindsey A. McAlarnen Jasmine George Ishaque P. Kadamberi Prachi Gupta Denise S. Uyar Elizabeth E. Hopp Holli Drendel Erin A. Bishop William H. Bradley Kathleen M. Bone Janet S. Rader Sunila Pradeep Pradeep Chaluvally-Raghavan Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance Cancers epithelial ovarian cancer cancer stemness spheroids PI3K/AKT signaling signaling addiction cancer cell line development |
| title | Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance |
| title_full | Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance |
| title_fullStr | Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance |
| title_full_unstemmed | Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance |
| title_short | Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance |
| title_sort | patient derived ovarian cancer spheroids rely on pi3k akt signaling addiction for cancer stemness and chemoresistance |
| topic | epithelial ovarian cancer cancer stemness spheroids PI3K/AKT signaling signaling addiction cancer cell line development |
| url | https://www.mdpi.com/2072-6694/14/4/958 |
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