Adipocyte-derived endotrophin promotes malignant tumor progression

Jiyoung Park, Philipp E. Scherer

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.

Original languageEnglish (US)
Pages (from-to)4243-4256
Number of pages14
JournalJournal of Clinical Investigation
Volume122
Issue number11
DOIs
StatePublished - Nov 1 2012

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Adipocytes
Breast Neoplasms
Growth
Neoplasms
Fibrosis
Epithelial-Mesenchymal Transition
Tumor Microenvironment
Stromal Cells
Adipose Tissue
Collagen
Endothelial Cells
Obesity
Macrophages
endotrophin
Inflammation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adipocyte-derived endotrophin promotes malignant tumor progression. / Park, Jiyoung; Scherer, Philipp E.

In: Journal of Clinical Investigation, Vol. 122, No. 11, 01.11.2012, p. 4243-4256.

Research output: Contribution to journalArticle

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