Human endotrophin as a driver of malignant tumor growth

Dawei Bu, Clair Crewe, Christine Kusminski, Ruth Gordillo, Alexandra L. Ghaben, Min Kim, Jiyoung Park, Hui Deng, Wei Xiong, Xiao Zheng Liu, Per Eystein Lønning, Nils Halberg, Adan Rios, Yujun Chang, Anneliese Gonzalez, Ningyan Zhang, Zhiqiang An, Philipp E Scherer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have previously reported that the carboxy-terminal proteolytic cleavage product of the COL6α3 chain that we refer to as "endotrophin" has potent effects on transformed mammary ductal epithelial cells in rodents. Endotrophin (ETP) is abundantly expressed in adipose tissue. It is a chemoattractant for macrophages, exerts effects on endothelial cells and through epithelialmesenchymal transition (EMT) enhances progression of tumor cells. In a recombinant form, human endotrophin exerts similar effects on human macrophages and endothelial cells as its rodent counterpart. It enhances EMT in human breast cancer cells and upon overexpression in tumor cells, the cells become chemoresistant. Here, we report the identification of endotrophin from human plasma. It is circulating at higher levels in breast cancer patients. We have developed neutralizing monoclonal antibodies against human endotrophin and provide evidence for the effectiveness of these antibodies to curb tumor growth and enhance chemosensitivity in a nude mouse model carrying human tumor cell lesions. Combined, the data validate endotrophin as a viable target for anti-tumor therapy for human breast cancer and opens the possibility for further use of these new reagents for anti-fibrotic approaches in liver, kidney, bone marrow and adipose tissue.

Original languageEnglish (US)
Article numbere125094
JournalJCI Insight
Volume4
Issue number9
DOIs
StatePublished - Jan 1 2019

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Growth
Neoplasms
Breast Neoplasms
Adipose Tissue
Rodentia
Endothelial Cells
Macrophages
Forensic Anthropology
Chemotactic Factors
Neutralizing Antibodies
Nude Mice
endotrophin
Breast
Bone Marrow
Epithelial Cells
Monoclonal Antibodies
Kidney
Bone and Bones
Antibodies
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human endotrophin as a driver of malignant tumor growth. / Bu, Dawei; Crewe, Clair; Kusminski, Christine; Gordillo, Ruth; Ghaben, Alexandra L.; Kim, Min; Park, Jiyoung; Deng, Hui; Xiong, Wei; Liu, Xiao Zheng; Lønning, Per Eystein; Halberg, Nils; Rios, Adan; Chang, Yujun; Gonzalez, Anneliese; Zhang, Ningyan; An, Zhiqiang; Scherer, Philipp E.

In: JCI Insight, Vol. 4, No. 9, e125094, 01.01.2019.

Research output: Contribution to journalArticle

Bu, D, Crewe, C, Kusminski, C, Gordillo, R, Ghaben, AL, Kim, M, Park, J, Deng, H, Xiong, W, Liu, XZ, Lønning, PE, Halberg, N, Rios, A, Chang, Y, Gonzalez, A, Zhang, N, An, Z & Scherer, PE 2019, 'Human endotrophin as a driver of malignant tumor growth', JCI Insight, vol. 4, no. 9, e125094. https://doi.org/10.1172/jci.insight.125094
Bu, Dawei ; Crewe, Clair ; Kusminski, Christine ; Gordillo, Ruth ; Ghaben, Alexandra L. ; Kim, Min ; Park, Jiyoung ; Deng, Hui ; Xiong, Wei ; Liu, Xiao Zheng ; Lønning, Per Eystein ; Halberg, Nils ; Rios, Adan ; Chang, Yujun ; Gonzalez, Anneliese ; Zhang, Ningyan ; An, Zhiqiang ; Scherer, Philipp E. / Human endotrophin as a driver of malignant tumor growth. In: JCI Insight. 2019 ; Vol. 4, No. 9.
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