Preclinical models of breast cancer: B6BC, a transplantable hormone receptor-positive C57BL/6 mouse cell line

Preclinical animal models are essential tools to develop and evaluate new anticancer treatments, notably immunotherapies, in which the complex interactions between cancer cells and the immune system need to be recapitulated.Consequently, the degree to which the preclinical model mimics certain disease aspects likely conditions its clinical translatability.In the context of breast cancer (BC), representative models should mimic key disease features such as the hormone receptor and ERBB2 status, as well as the composition of the tumor immune infiltrate.However, such information is generally limited notably for transplantable mouse cancer cell lines, which tend to be poorly characterized with respect to their histopathological subtype and to the tumor microenvironment that they generate, especially if they fail to strive after injection into syngeneic hosts [1].Despite the fact that hormone receptor-positive BC (which express estrogen receptor, ER, and/or progesterone receptor, PR) are among the most common woman cancers, there have been no hormone receptor-positive cell lines that could be transplanted into immunocompetent C57BL/6 mice, the most frequently used inbred mouse strain [2].To fill this gap, we established the first ER + mammary carcinoma cell line transplantable into syngeneic C57BL/6 females, called B6BC cells.Such B6BC cells were generated from a tumor of a hormone-dependent carcinogeninduced BC model in C57BL/6 females [3].We extensively characterized the cancer cell-intrinsic and tumor-infiltrating immune cell properties of B6BC cell-derived tumors, while comparing them to tumors arising from several other commonly used cell lines in the setting of non-resected advanced disease, as well as to the original tumor they derived from [3,4].In this Spotlight we focus on the comparison of ER + B6BC tumors inoculated into C57BL/6 mice with ER + TS/A tumors developing in BALB/C females and ER -E0771 (also spelled EO771) from C57BL/6 mice (Table 1).We first generated and selected B6BC cells among other eight mammary carcinoma cell lines, based on two criteria, namely (i) transplantability to immunocompetent C57BL/6 mice and (ii) expression of high levels of both ER and PR.When inoculated into syngeneic hosts, B6BC tumors exhibited a spindle-like shape morphology and retained (although downregulated) ER expression but completely lost PR.This contrasted with the epitheloidspindle morphology of TS/A cells expressing ER but not PR and that of pleomorphic-anaplastic-like E0771 cells that were negative