Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts
Abstract To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/834953b117d94032b1c80331230a11b1 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:834953b117d94032b1c80331230a11b1 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:834953b117d94032b1c80331230a11b12021-12-02T11:52:33ZTargeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts10.1038/s41598-017-09020-82045-2322https://doaj.org/article/834953b117d94032b1c80331230a11b12017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09020-8https://doaj.org/toc/2045-2322Abstract To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor — JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy.Jindong ShiJingjing FengJuan XieZhoufang MeiTianyun ShiShengmei WangYong DuGong YangYougen WuXiaojiao ChengShanqun LiLiming ZhuChung S. YangShuiping TuZhijun JieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Jindong Shi Jingjing Feng Juan Xie Zhoufang Mei Tianyun Shi Shengmei Wang Yong Du Gong Yang Yougen Wu Xiaojiao Cheng Shanqun Li Liming Zhu Chung S. Yang Shuiping Tu Zhijun Jie Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| description |
Abstract To investigate the role of TGF-β and IL-6 in myofibroblasts (MFs) — lung cancer cell interactions, lung cancer cells (Lewis and CTM-167 cell lines) were stimulated by IL-6, MF-conditioned medium (MF-CM) or MFs, with or without TGF-β signaling inhibitor — SB431542 and/or JAK2/STAT3 inhibitor — JSI-124. MFs were stimulated by TGF-β, cancer cell-CM or cancer cells, with or without SB431542 and JSI-124. Cell proliferation, the levels of cytokines, expression of mRNA and protein were determined. Mice bearing xenograft tumors were intraperitoneally treated with SB431542 or JSI-124 and monitored for up to 45 days. In co-culture systems, MFs secreted high levels of IL-6, while cancer cells produced high levels of TGF-β. Recombinant IL-6 and MF-CM activated STAT3 and upregulated TGF-β in cancer cells. In contrast, cancer cell-CM or TGF-β stimulated MFs to produce IL-6. Blockade of JAK2/STAT3 and TGF-β signaling by specific inhibitors significantly inhibited cell proliferation in vitro and tumor growth in vivo of lung cancer cells. Our study demontrated that the TGF-β and IL-6/JAK2/STAT3 signaling pathways form a positive feedback signaling loop that mediated the interactions between MFs and lung cancer cells. Targeted inhibiton of this signaling loop could be a new approach for lung cancer prevention and therapy. |
| format |
article |
| author |
Jindong Shi Jingjing Feng Juan Xie Zhoufang Mei Tianyun Shi Shengmei Wang Yong Du Gong Yang Yougen Wu Xiaojiao Cheng Shanqun Li Liming Zhu Chung S. Yang Shuiping Tu Zhijun Jie |
| author_facet |
Jindong Shi Jingjing Feng Juan Xie Zhoufang Mei Tianyun Shi Shengmei Wang Yong Du Gong Yang Yougen Wu Xiaojiao Cheng Shanqun Li Liming Zhu Chung S. Yang Shuiping Tu Zhijun Jie |
| author_sort |
Jindong Shi |
| title |
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| title_short |
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| title_full |
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| title_fullStr |
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| title_full_unstemmed |
Targeted blockade of TGF-β and IL-6/JAK2/STAT3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| title_sort |
targeted blockade of tgf-β and il-6/jak2/stat3 pathways inhibits lung cancer growth promoted by bone marrow-derived myofibroblasts |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/834953b117d94032b1c80331230a11b1 |
| work_keys_str_mv |
AT jindongshi targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT jingjingfeng targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT juanxie targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT zhoufangmei targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT tianyunshi targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT shengmeiwang targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT yongdu targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT gongyang targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT yougenwu targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT xiaojiaocheng targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT shanqunli targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT limingzhu targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT chungsyang targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT shuipingtu targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts AT zhijunjie targetedblockadeoftgfbandil6jak2stat3pathwaysinhibitslungcancergrowthpromotedbybonemarrowderivedmyofibroblasts |
| _version_ |
1718394993843896320 |