WCRC-25: A novel luminal Invasive Lobular Carcinoma cell line model

Abstract

Breast cancer is broadly divided histologically into no special type (NST) and special subtypes, of which invasive lobular carcinoma (ILC) is the most common. ILC is distinguished by discohesive, single-file growth from loss of E-cadherin (CDH1). Few ILC cell lines exist, limiting mechanistic study of this understudied disease. Here we describe WCRC-25, a novel ILC cell line established from a pleural effusion of a patient with metastatic ILC. While WCRC-25 lacks ER expression, it is molecularly defined as luminal with Her2-like features, and shows anchorage-independent growth and haptotactic migration toward Collagen I. Sequencing identified a CDH1 Q706* truncating mutation alongside FOXA1, CTCF, BRCA2 and TP53 mutations shared with the patient's metastases, while copy-number and optical genome mapping revealed structural rearrangements typical of ILC. Transcriptomic AKT-pathway signatures predicted, and cell-based assays confirmed, sensitivity to PI3K/AKT inhibition. WCRC-25 also engrafted and spontaneously metastasized in vivo. WCRC-25 is a valuable new tool for dissecting ILC biology and therapeutic vulnerabilities.