Open AccessSuppression of IL‐8‐Src signalling axis by 17β‐estradiol inhibits human mesenchymal stem cells‐mediated gastric cancer invasion
Author(s) -
Liu ChungJung,
Kuo FuChen,
Wang ChiuLin,
Kuo ChaoHung,
Wang Sophie S.W.,
Chen ChiaoYun,
Huang YawBin,
Cheng KuangHung,
Yokoyama Kazunari K.,
Chen ChunLin,
Lu ChienYu,
Wu DengChyang
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12786
Subject(s) - mesenchymal stem cell , cancer research , proto oncogene tyrosine protein kinase src , cancer , cancer cell , biology , microbiology and biotechnology , medicine , signal transduction
Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells ( BMMSC s) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSC s‐mediated human gastric cancer invasive motility. We founded that HBMMSC s notably secrete interleukin‐8 ( IL ‐8) protein. Administration of IL ‐8 specific neutralizing antibody significantly inhibits HBMMSC s‐mediated gastric cancer motility. Treatment of recombinant IL ‐8 soluble protein confirmed the role of IL ‐8 in mediating HBMMSC s‐up‐regulated cell motility. IL ‐8 up‐regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β ‐estradiol inhibit HBMMSCS ‐induced cell motility via suppressing activation of IL 8‐Src signalling in human gastric cancer cells. 17β‐estradiol inhibits IL 8‐up‐regulated Src downstream target proteins including p‐Cas, p‐paxillin, p‐ ERK 1/2, p‐ JNK 1/2, MMP 9, tPA and uPA . These results suggest that 17β‐estradiol significantly inhibits HBMMSCS ‐induced invasive motility through suppressing IL 8‐Src signalling axis in human gastric cancer cells.