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The cell-cell interaction between tumor-associated macrophages and small cell lung cancer cells is involved in tumor progression via STAT3 activation.

Authors :
Iriki, Toyohisa
Ohnishi, Koji
Fujiwara, Yukio
Horlad, Hasita
Saito, Yoichi
Pan, Cheng
Ikeda, Koei
Mori, Takeshi
Suzuki, Makoto
Ichiyasu, Hidenori
Kohrogi, Hirotsugu
Takeya, Motohiro
Komohara, Yoshihiro
Source :
Lung Cancer (01695002). Apr2017, Vol. 106, p22-32. 11p.
Publication Year :
2017

Abstract

Objectives Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. It is well known that various stromal cells, including macrophages, play a role in tumor progression in several types of malignant tumors; however, the significance of tumor-associated macrophages (TAMs) in SCLC has not been fully elucidated. Signal transducer and activator of transcription 3 (STAT3) is a molecule well-known to be related to tumor progression. In the present study, we investigated the relationship of TAMs and SCLC cells to test the hypothesis that TAMs induce tumor progression in SCLC via STAT3 activation. Materials and methods We performed immunohistochemical analysis using surgically resected tumor specimens and in vitro co-culture experiments using human SCLC cell lines and human monocyte-derived macrophages. Results We first demonstrated via immunostaining that STAT3 activation in tumor cells was predominantly observed in the peripheral areas of tumor nests existing near TAMs in stroma. The indirect co-culture of SCLC cells and macrophages induced STAT3 activation in both cell types, and macrophage-derived culture supernatant (CS) significantly activated STAT3 in SCLC cells. Macrophage-derived CS induced tumor cell proliferation and invasion via STAT3 activation. In addition, chemo-resistance and sphere formation were also increased by macrophage-derived CS. Macrophage-derived interleukin-6 and CC chemokine ligand 4 (CCL4/MIP-1β) were suggested to be associated with STAT3 activation in SCLC cells. CS-induced STAT3 activation in SCLC cells was suppressed by anti-IL-6 receptor antibody, but not by anti-CCL4/MIP-1β antibody. Conclusion These results suggest that TAMs are likely involved in SCLC progression via STAT3 activation and TAM-derived IL-6 is indicated to be one of molecules related to STAT3 activation in SCLC cells. Thus, the cell-cell interaction between TAMs and SCLC cells might be a target for therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01695002
Volume :
106
Database :
Academic Search Index
Journal :
Lung Cancer (01695002)
Publication Type :
Academic Journal
Accession number :
121753951
Full Text :
https://doi.org/10.1016/j.lungcan.2017.01.003