Murine mammary tumor cells with a claudin-low genotype

Abstract

BackgroundMolecular classification of human breast cancers has identified at least 5 distinct tumor subtypes; luminal A, luminal B, Her2-enriched, basal-like and claudin-low. The claudin-low subtype was identified in 2007 and is characterized by low expression of luminal differentiation markers and claudins 3, 4 and 7 and high levels of mesenchymal markers. Claudin-low tumors have a reported prevalence of 7-14% and these tumors have a poor prognosis.ResultsIn this study we report the characterization of several cell lines established from mammary tumors that develop in MTB-IGFIR transgenic mice. Two lines, RM11A and RJ348 present with histological features and gene expression patterns that resemble claudin-low breast tumors. Specifically, RM11A and RJ348 cells express high levels of the mesenchymal genes Zeb1, Zeb2, Twist1 and Twist2 and very low levels of E-cadherin and claudins 3, 4 and 7. The RM11A and RJ348 cells are also highly tumorigenic when re-introduced into the mammary fat pad of mice.ConclusionsMammary tumor cells established from MTB-IGFIR transgenic mice can be used as in vitro and in vivo model systems to further our understanding of the poorly characterized, claudin-low, breast cancer subtype.

Dietary Energy Balance Modulates Epithelial-to-Mesenchymal Transition and Tumor Progression in Murine Claudin-Low and Basal-like Mammary Tumor Models

“…In contrast, E-Wnt cells clustered tightly with mammary tumors from C3-Tag transgenic mice, an established model of basal-like breast cancer (5,23,24). M-Wnt cells, relative to E-Wnt cells, had significantly lower expression of E-cadherin and higher expression of N-cadherin, fibronectin, and vimentin (p<0.001, each gene) (Figure 4A, upper panel).…”

“…Xenograft models are limited for studying links between energy balance, TICs and breast cancer because immunodeficient mice have aberrant mammary gland development, lack normal immune/inflammatory responses, and resist developing DIO and CR phenotypes. Syngeneic transplant models of claudin-low breast cancer derived from p53-null or IGF-1 receptor-overexpressing mouse mammary tumors (23,26) appear poorly suited for modeling energy balance/breast cancer links given the established roles of p53 and IGF-1 pathways in the anticancer effects of many interventions (27-29). Our M-Wnt transplant model of claudin-low mammary cancer overcomes many existing limitations by using a) cells derived from a spontaneous MMTV-Wnt-1 mouse mammary tumor that, like basal-like breast cancers in women, are responsive to CR and obesity (17,30), and b) a wild-type, syngeneic host with normal immune function, mammary gland development and metabolic responses to energy balance modulation.…”

“…The M-Wnt cell line is among the few reported murine mammary cancer cell lines to closely mimic the pathology and molecular profile of human claudin-low breast tumors (4,23,26). M-Wnt cells have mesenchymal morphology, are stably enriched in putative TICs (>60% CD44 high /CD24 low , with high ALDH activity), display molecular signatures of EMT resembling human claudin-low breast tumors, readily form mammospheres in suspension culture, are highly invasive and migratory, and generate ER-negative, PR-negative claudin-low mammary tumors when as few as 50 cells are injected orthotopically.…”

Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells

“…To determine whether the tumor cells themselves were producing OPN, cell lines derived from different MTB-IGFIR mammary tumors were evaluated. The two best characterized lines are RJ345 cells (which have characteristics similar to PMT tumors in MTB-IGFIR transgenic mice) and RJ348 cells (which have characteristics similar to RST tumors in MTB-IGFIR transgenic mice) [ 34 , 38 – 40 ]. As shown in Table 2 , RJ348 cells expressed higher levels of Spp1 than RJ345 cells.…”

“…A number of cell lines have been generated from these tumors. RJ345 cells share characteristics with the luminal/basal like tumors while RJ348 and RM11A share characteristics with the claudin-low tumors [ 34 , 35 ]…”