Suppression of IL‐8‐Src signalling axis by 17β‐estradiol inhibits human mesenchymal stem cells‐mediated gastric cancer invasion |
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| Authors: | Chung‐Jung Liu Fu‐Chen Kuo Chiu‐Lin Wang Chao‐Hung Kuo Sophie S.W. Wang Chiao‐Yun Chen Yaw‐Bin Huang Kuang‐Hung Cheng Kazunari K. Yokoyama Chun‐Lin Chen Chien‐Yu Lu Deng‐Chyang Wu |
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| Affiliation: | 1. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;2. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan;3. School of Medicine, College of Medicine, I‐Shou University, Kaohsiung, Taiwan;4. Department of Obstetrics and Gynecology, E‐Da Hospital, Kaohsiung, Taiwan;5. Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao‐Kang Hospital, Kaohsiung, Taiwan;6. Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;7. Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;8. Department of Radiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;9. Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan;10. Institute of Biomedical Sciences, National Sun Yat‐Sen University, Kaohsiung, Taiwan;11. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;12. Department of Biological Science, National Sun Yat‐sen University, Kaohsiung, Taiwan;13. Department of Internal Medicine, Kaohsiung Municipal Ta‐Tung Hospital, Kaohsiung, Taiwan |
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| Abstract: | 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 (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs‐mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin‐8 (IL‐8) protein. Administration of IL‐8 specific neutralizing antibody significantly inhibits HBMMSCs‐mediated gastric cancer motility. Treatment of recombinant IL‐8 soluble protein confirmed the role of IL‐8 in mediating HBMMSCs‐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 IL8‐Src signalling in human gastric cancer cells. 17β‐estradiol inhibits IL8‐up‐regulated Src downstream target proteins including p‐Cas, p‐paxillin, p‐ERK1/2, p‐JNK1/2, MMP9, tPA and uPA. These results suggest that 17β‐estradiol significantly inhibits HBMMSCS‐induced invasive motility through suppressing IL8‐Src signalling axis in human gastric cancer cells. |
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| Keywords: | 17β ‐estradiol mesenchymal stem cell IL‐8 Src gastric cancer cell invasion motility |
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