Open AccessLipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion
Author(s) -
Villodre Emilly S.,
Hu Xiaoding,
Larson Richard,
Finetti Pascal,
Gomez Kristen,
Balema Wintana,
Stecklein Shane R.,
SantiagoSanchez Ginette,
Krishnamurthy Savitri,
Song Juhee,
Su Xiaoping,
Ueno Naoto T.,
Tripathy Debu,
Van Laere Steven,
Bertucci François,
VivasMejía Pablo,
Woodward Wendy A.,
Debeb Bisrat G.
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13074
Subject(s) - inflammatory breast cancer , lipocalin , cancer research , carcinogenesis , metastasis , biology , breast cancer , cancer , cell culture , medicine , immunology , genetics
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 vs 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.