Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells
Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells
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间充质干细胞引发的自主和细胞间趋化因子信号传导调节未分化胃癌细胞的迁移
DOI：
10.1111/gtc.12933
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发表时间：
2022
期刊：
影响因子：
2.1
通讯作者：
Kamizaki Koki
中科院分区：
文献类型：
--
作者：
Okamoto Daiki;Yamauchi Natsuko;Takiguchi Gosuke;Nishita Michiru;Kakeji Yoshihiro;Minami Yasuhiro;Kamizaki Koki
越来越多的证据表明，骨髓（BM）来源的间充质干细胞（MSCs）在调节各种类型癌症的进展中起着关键作用。我们之前已经证明MSCs中的Wnt5a‐Ror2信号传导诱导CXCL16的表达，并且MSCs分泌的CXCL16随后与未分化的胃癌细胞系MKN45细胞表面的同源受体CXCR6结合，最终导致MKN45细胞的增殖和迁移。然而，目前尚不清楚是否有其他细胞因子参与调节胃癌的进展。在这里，我们发现CXCL16‐CXCR6信号也通过细胞自主机制在MSCs中被激活，导致CCL5的表达上调。我们进一步发现CCL5的受体CCR1和CCR3在MKN45细胞表面表达，MSCs分泌的CCL5可能通过与CCR1/CCR3的结合促进MKN45细胞的迁移。这些数据表明，在MSCs中激活的细胞自主CXCL16‐CXCR6信号可以上调CCL5的表达，并且随后通过细胞间机制激活MKN45细胞中的CCL5‐CCR1/3信号可以促进MKN45细胞的迁移。总的来说，这些发现假设存在从MSCs发出的精心安排的趋化因子信号，以调节未分化胃癌细胞的进展。
Accumulating evidence demonstrates that bone marrow (BM)‐derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a‐Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer. Here, we show that CXCL16‐CXCR6 signaling is also activated in MSCs through cell‐autonomous machinery, leading to upregulated expression of CCL5. We further show that CCR1 and CCR3, receptors of CCL5, are expressed on the surface of MKN45 cells, and that CCL5 secreted from MSCs promotes migration of MKN45 cells presumably via its binding to CCR1/CCR3. These data indicate that cell‐autonomous CXCL16‐CXCR6 signaling activated in MSCs upregulates expression of CCL5, and that subsequent activation of CCL5‐CCR1/3 signaling in MKN45 cells through intercellular machinery can promote migration of MKN45 cells. Collectively, these findings postulate the presence of orchestrated chemokine signaling emanated from MSCs to regulate progression of undifferentiated gastric cancer cells.
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DOI：
--
发表时间：
2021
期刊：
Oncol. Rep
影响因子：
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作者：
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