High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer

Anita Rogic, Ila Pant, Luca Grumolato, Ruben Fernandez-Rodriguez, Andrew Edwards, Suvendu Das, Aaron Sun, Shen Yao, Rui Qiao, Shabnam Jaffer, Ravi Sachidanandam, Guray Akturk, Rosa Karlic, Mihaela Skobe, Stuart A. Aaronson

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Inflammatory Breast Cancer (IBC) is a highly aggressive malignancy with distinct clinical and histopathological features whose molecular basis is unresolved. Here we describe a human IBC cell line, A3250, that recapitulates key IBC features in a mouse xenograft model, including skin erythema, diffuse tumor growth, dermal lymphatic invasion, and extensive metastases. A3250 cells express very high levels of the CCL2 chemokine and induce tumors enriched in macrophages. CCL2 knockdown leads to a striking reduction in macrophage densities, tumor proliferation, skin erythema, and metastasis. These results establish IBC-derived CCL2 as a key factor driving macrophage expansion, and indirectly tumor growth, with transcriptomic analysis demonstrating the activation of multiple inflammatory pathways. Finally, primary human IBCs exhibit macrophage infiltration and an enriched macrophage RNA signature. Thus, this human IBC model provides insight into the distinctive biology of IBC, and highlights potential therapeutic approaches to this deadly disease.

Original languageEnglish
Article number6889
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

Fingerprint

Dive into the research topics of 'High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer'. Together they form a unique fingerprint.

Cite this