Exosomes are nano-vesicles transporting bioactive material between cells. This study explored the prognostic association of exosomal TGF-beta 1 with lymph node (LN) metastasis of gastric cancer (GC). TGF-beta 1 expressions in the exosomes isolated from the gastroepiploic veins of 61 GC patients analyzed by ELISA. The regulatory T (Treg) cells in celiac LNs of gastric cancer analyzed by immunohistochemistry. Exosomal TGF-beta 1 expression and the ratio of Treg cells in draining LNs were both significantly associated with pathological stages and LN metastasis of gastric cancer. Besides, the exosomal TGF-beta 1 expression and Treg proportion in LN were also significantly correlated in gastric cancer patients. Recombinant TGF-beta 1 and exosomes isolated from GC patients were used to induce FOXP3+ Treg cells from naive T cells in vitro. Compared to the control, recombinant TGF-beta 1 induced more CD25 (41%), FOXP3 (19%) and CTLA-4 (47%), while reduced CD45RA expression by 38% in primary naive T cell cultures (p< 0.01). Exosomes treatment induced more CD25 and 45% higher CTLA-4 expression, and increased 29% higher of CD45RAnegative cells than recombinant TGF-beta 1 did (p< 0.01). Adding TGF-beta 1 neutralizing antibody partially abrogated the effects of exosomes on Treg induction. Our study showed exosomal TGF-beta 1 related to lymph node metastasis and the ratio of Treg cells in lymph nodes of gastric cancers. Exosomes from gastric cancer patients could induce Treg cells formation through the effect of TGF-beta 1.
机构:
Ehime Univ, Dept Mol Med Pathogenesis, Grad Sch Med, Toon, Ehime 7910295, Japan
Japan Sci & Technol Agcy JST, Toon, Ehime 7910295, JapanEhime Univ, Dept Mol Med Pathogenesis, Grad Sch Med, Toon, Ehime 7910295, Japan
Imamura, Takeshi
Hikita, Atsuhiko
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Ehime Univ, Dept Mol Med Pathogenesis, Grad Sch Med, Toon, Ehime 7910295, Japan
Japan Sci & Technol Agcy JST, Toon, Ehime 7910295, JapanEhime Univ, Dept Mol Med Pathogenesis, Grad Sch Med, Toon, Ehime 7910295, Japan
Hikita, Atsuhiko
Inoue, Yasumichi
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Nagoya City Univ, Dept Drug Metab & Disposit, Grad Sch Pharmaceut Sci, Nagoya, Aichi 4678603, JapanEhime Univ, Dept Mol Med Pathogenesis, Grad Sch Med, Toon, Ehime 7910295, Japan
机构:
Tokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Tokyo Univ Pharm & Life Sci, Lab Stem Cell Regulat, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Fukasawa, Kunpei
Hanada, Kako
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Tokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Tokyo Univ Pharm & Life Sci, Lab Stem Cell Regulat, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Hanada, Kako
Ichikawa, Kei
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Tokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Ichikawa, Kei
Hirashima, Masanori
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Niigata Univ, Grad Sch Med & Dent Sci, Div Pharmacol, Chuo Ku, 1-757 Asahimachi Dori, Niigata 9518510, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Hirashima, Masanori
Takagi, Takahiro
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Tokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Takagi, Takahiro
Itoh, Susumu
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Showa Pharmaceut Univ, Lab Biochem, 3-3165 Higashi Tamagawagakuen, Machida, Tokyo 1948543, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Itoh, Susumu
Watabe, Testuro
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Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Biochem, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138549, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Watabe, Testuro
Itoh, Fumiko
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机构:
Tokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
Tokyo Univ Pharm & Life Sci, Lab Stem Cell Regulat, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, JapanTokyo Univ Pharm & Life Sci, Lab Cardiovasc Med, 1432-1 Horinouchi, Hachioji, Tokyo 19250392, Japan
机构:
Capital Med Univ, Dept Gynecol & Obstet, Beijing Chaoyang Hosp, Beijing 100020, Peoples R ChinaCapital Med Univ, Dept Gynecol & Obstet, Beijing Chaoyang Hosp, Beijing 100020, Peoples R China
Zhu, Lei
Yu, Chun-Ling
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Daqing Oilfield Gen Hosp, Dept Gynecol Clin, Daqing 163000, Heilongjiang, Peoples R ChinaCapital Med Univ, Dept Gynecol & Obstet, Beijing Chaoyang Hosp, Beijing 100020, Peoples R China
Yu, Chun-Ling
Zheng, Yuwei
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机构:
Fudan Univ, Dept Pathol, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
Fudan Univ, Inst Pathol, Shanghai 200032, Peoples R ChinaCapital Med Univ, Dept Gynecol & Obstet, Beijing Chaoyang Hosp, Beijing 100020, Peoples R China