Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance. Cancers (Basel) 2022 Feb 15;14(4)
Date
02/26/2022Pubmed ID
35205706Pubmed Central ID
PMC8870411DOI
10.3390/cancers14040958Scopus ID
2-s2.0-85124460063 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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.
Author List
Parashar D, Geethadevi A, Mittal S, McAlarnen LA, George J, Kadamberi IP, Gupta P, Uyar DS, Hopp EE, Drendel H, Bishop EA, Bradley WH, Bone KM, Rader JS, Pradeep S, Chaluvally-Raghavan PAuthors
Erin Bishop MD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinKathleen M. Bone PhD Associate Professor in the Pathology department at Medical College of Wisconsin
William H. Bradley MD Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Anjali Geethadevi PHD Research Scientist I in the Obstetrics and Gynecology department at Medical College of Wisconsin
Elizabeth E. Hopp MD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Lindsey A. McAlarnen MD Gynecology Oncology Fellow in the Obstetrics and Gynecology department at Medical College of Wisconsin
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Denise S. Uyar MD Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
