Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC versus non-IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non-IBC cell lines. High expression was associated with poor-prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro, and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC.
Background Inflammatory breast cancer (IBC) is a clinical diagnosis. Here, we examined the association of a “classic” triad of clinical signs, swollen involved breast, nipple change, and diffuse skin change, with overall survival (OS). Method Breast medical photographs from patients enrolled on a prospective IBC registry were scored by two independent reviewers as classic (triad above), not classic, and difficult to assign. Chi‐squared test, Fisher's exact test, and Wilcoxon rank‐sum test were used to assess differences between patient groups. Kaplan–Meier estimates and the log‐rank test and Cox proportional hazard regression were used to assess the OS. Results We analyzed 245 IBC patients with median age 54 (range 26–81), M0 versus M1 status (157 and 88 patients, respectively). The classic triad was significantly associated with smoking, post‐menopausal status, and metastatic disease at presentation ( p = 0.002, 0.013, and 0.035, respectively). Ten‐year actuarial OS for not classic and difficult to assign were not significantly different and were grouped for further analyses. Ten‐year OS was 29.7% among patients with the classic sign triad versus 57.2% for non‐classic ( p < 0.0001). The multivariate Cox regression model adjusting for clinical staging ( p < 0.0001) and TNBC status (<0.0001) demonstrated classic presentation score significantly associated with poorer OS time (HR 2.6, 95% CI 1.7–3.9, p < 0.0001). Conclusions A triad of classic IBC signs independently predicted OS in patients diagnosed with IBC. Further work is warranted to understand the biology related to clinical signs and further extend the understanding of physical examination findings in IBC.
Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC versus non-IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non-IBC cell lines. High expression was associated with poor-prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced proliferation, colony formation, migration, and cancer stem cell populations in vitro, and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.