TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
TP53失活是骨肉瘤(OS)发生中的关键事件,也是其侵袭性的基础,但其在肿瘤-免疫相互作用中的作用仍知之甚少。
英文原题:Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells.
在过去十年中,基于间充质干细胞(MSC)对癌细胞独特的趋向性,利用 MSC 的肿瘤靶向治疗迅速扩展。
过去十年,基于间充质干细胞(MSC)对癌细胞具有独特趋向性的肿瘤靶向治疗迅速发展。尽管不同组织来源的MSC在形态、免疫表型和体外多向分化潜能方面相似,其生物学行为不一定相同。因此,筛选对癌细胞趋化性最强的MSC很重要。本研究从脂肪、脐带、羊膜和绒毛膜等不同人体组织分离MSC。采用CCK-8、ELISA和Transwell侵袭实验测量人MSC对宫颈癌细胞的趋化性,并通过Western blot探索潜在机制。不同来源MSC被宫颈癌细胞募集的能力不同,其中绒毛膜来源MSC(CD-MSC)趋向性最强。宫颈癌细胞高分泌CXCL12,同时所有MSC均表达CXCR4;CD-MSC的CXCR4水平最高。结果提示,CXCL12/CXCR4通路参与不同MSC对宫颈癌细胞的趋化差异。本研究提出,CXCR4表达最高的CD-MSC是宫颈癌靶向治疗中有前景的治疗载体。
In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical cancer.
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