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 () and Stuart A. Aaronson ()
Additional contact information
Anita Rogic: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Ila Pant: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Luca Grumolato: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Ruben Fernandez-Rodriguez: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Andrew Edwards: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Suvendu Das: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Aaron Sun: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Shen Yao: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Rui Qiao: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Shabnam Jaffer: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Ravi Sachidanandam: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Guray Akturk: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Rosa Karlic: University of Zagreb
Mihaela Skobe: Laboratory of Cancer Lymphangiogenesis, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
Stuart A. Aaronson: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27108-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27108-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27108-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().