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Interleukin-22 promotes development of malignant lesions in a mouse model of spontaneous breast cancer.
- Source :
-
Molecular oncology [Mol Oncol] 2020 Jan; Vol. 14 (1), pp. 211-224. Date of Electronic Publication: 2019 Dec 04. - Publication Year :
- 2020
-
Abstract
- Interleukin (IL)-22 is recognized as a tumor-supporting cytokine and is implicated in the proliferation of multiple epithelial cancers. In breast cancer, the current knowledge of IL-22 function is based on cell line models and little is known about how IL-22 affects the tumor initiation, proliferation, invasion, and metastasis in the in vivo system. Here, we investigated the tumor stage-specific function of IL-22 in disease development by evaluating the stage-by-stage progression of breast cancer in an IL-22 knockout spontaneous breast cancer mouse model. We found that among all the stages, IL-22 is specifically upregulated in tumor microenvironment (TME) during the malignant transformation stage of breast tumor progression. The deletion of IL-22 gene leads to the arrest of malignant transition stage, and reduced invasion and tumor burden. Administration of recombinant IL-22 in the TME does not influence in vivo tumor initiation and proliferation but only promotes malignant transformation of cancer cells. Mechanistically, deletion of IL-22 gene causes downregulation of epithelial-to-mesenchymal transition (EMT)-associated transcription factors in breast tumors, suggesting EMT as the mechanism of regulation of malignancy by IL-22. Clinically, in human breast tumor tissues, increased number of IL-22 <superscript>+</superscript> cells in the TME is associated with an aggressive phenotype of breast cancer. For the first time, this study provides an insight into the tumor stage-specific function of IL-22 in breast tumorigenesis.<br /> (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Antigens, Polyomavirus Transforming genetics
Antigens, Polyomavirus Transforming metabolism
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Cell Transformation, Neoplastic genetics
Disease Progression
Female
Gene Expression Regulation, Neoplastic genetics
Humans
Immunohistochemistry
Interleukins administration & dosage
Interleukins genetics
Mammary Neoplasms, Experimental genetics
Mammary Neoplasms, Experimental pathology
Mice
Mice, Knockout
Neoplasm Invasiveness genetics
Neoplasm Metastasis genetics
Neoplasm Staging
Recombinant Proteins
Tissue Array Analysis
Up-Regulation
Interleukin-22
Breast Neoplasms metabolism
Cell Movement genetics
Cell Proliferation genetics
Epithelial-Mesenchymal Transition genetics
Interleukins metabolism
Mammary Neoplasms, Experimental metabolism
Tumor Microenvironment genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-0261
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular oncology
- Publication Type :
- Academic Journal
- Accession number :
- 31725949
- Full Text :
- https://doi.org/10.1002/1878-0261.12598