Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer

Abnormal differentiation of myeloid cells is one of the hallmarks of cancer. However, the molecular mechanisms of this process remain elusive. In this study, we investigated the effect of tumor-derived factors on Janus kinase (Jak)/STAT signaling in myeloid cells during their differentiation into de...

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Veröffentlicht in:The Journal of immunology (1950) Jg. 172; H. 1; S. 464
Hauptverfasser: Nefedova, Yulia, Huang, Mei, Kusmartsev, Sergei, Bhattacharya, Raka, Cheng, Pingyan, Salup, Raoul, Jove, Richard, Gabrilovich, Dmitry
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.01.2004
Schlagworte:
Animals
Cell Aggregation - immunology
Cell Differentiation - immunology
Cell Division - immunology
Cell Line, Tumor
Colonic Neoplasms - enzymology
Colonic Neoplasms - immunology
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Dendritic Cells - enzymology
Dendritic Cells - metabolism
Dendritic Cells - pathology
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Female
Growth Inhibitors - physiology
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - pathology
Janus Kinase 2
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Myeloid Cells - metabolism
Myeloid Cells - pathology
Neoplasm Proteins - physiology
NIH 3T3 Cells
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins
Signal Transduction - immunology
STAT3 Transcription Factor
Trans-Activators - metabolism
Trans-Activators - physiology
Up-Regulation - immunology
ISSN:0022-1767
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Zusammenfassung:Abnormal differentiation of myeloid cells is one of the hallmarks of cancer. However, the molecular mechanisms of this process remain elusive. In this study, we investigated the effect of tumor-derived factors on Janus kinase (Jak)/STAT signaling in myeloid cells during their differentiation into dendritic cells. Tumor cell conditioned medium induced activation of Jak2 and STAT3, which was associated with an accumulation of immature myeloid cells. Jak2/STAT3 activity was localized primarily in these myeloid cells, which prevented the differentiation of immature myeloid cells into mature dendritic cells. This differentiation was restored after removal of tumor-derived factors. Inhibition of STAT3 abrogated the negative effects of these factors on myeloid cell differentiation, and overexpression of STAT3 reproduced the effects of tumor-derived factors. Thus, this is a first demonstration that tumor-derived factors may affect myeloid cell differentiation in cancer via constitutive activation of Jak2/STAT3.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0022-1767
DOI:10.4049/jimmunol.172.1.464