Abstract
Abstract
Breast cancer is categorized by the molecular and histologic presentation of the tumor; with the major histologic subtypes observed in patients being Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC). ILC are characterized by growth in a single file discohesive manner with stromal infiltration attributed to their hallmark loss of E-cadherin. The lower incidence of ILC, relative to IDC, resulted in this subtype being understudied in the field. The Cancer Cell Line Encyclopedia (CCLE) currently only lists 2 ILC cell lines; emphasizing the need to expand the inventory of models available to researchers. To that end, here we report the successful establishment and characterization of a novel ILC cell line from a metastatic pleural aspirate from a postmenopausal Caucasian woman with ER+ metastatic ILC. The patient underwent a bilateral mastectomy, several pleural fluid aspirations and multiple treatment changes as her disease progressed until she succumbed to the disease. Various cell culture methods were attempted with the pleural aspirate and a standard practice of DMEM supplemented with 10% FBS in normoxic conditions was deemed effective. A cell line was developed, WCRC-25 which is ER-. WCRC-25 appears to be E2 unresponsive in vitro and is morphologically larger than other ILC cells currently in use, namely, MDA-MB-134, BCK4 and IPH-926, while exhibiting better adherence to 2D plates and a less rounded morphology. Sequencing revealed a CDH1 Q706 truncating mutation in the cells, which was also observed in the patient’s cfDNA with its enrichment increasing over time, supporting elevated disease burden. RNA-seq analysis comparing the primary tumor to metastases and the cell line reveal a signature for cell cycle progression and Akt signaling. To assess targetability, we subjected WCRC-25 to AZD5363 and Alpelisib which confirmed WCRC-25 as susceptible to PI3K/Akt signaling inhibition. Finally, we generated mouse xenograft models of WCRC-25 through mammary fat pad injection and observed small, but palpable tumors and metastasis to several sites. In conclusion, we report WCRC-25 as a novel ILC cell line with much promise as an invaluable research tool to advance our understanding of ILC and its therapeutic vulnerabilities.
Citation Format: Ashuvinee Elangovan, Emily A Bossart, Ahmed Basudan, Nilgun Tasdemir, Osama Shiraz Shah, Kai Ding, Carolin Meier, Tanya Heim, Lori Miller, Tiantong Liu, Shannon L Puhalla, Grzegorz Gurda, Peter C Lucas, Priscilla F McAuliffe, Jennifer M Atkinson, Adrian V Lee, Steffi Oesterreich. Wcrc-25: A novel luminal invasive lobular carcinoma cell line model [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-03.