摘要
血管生成拟态(vasculogenic mimicry,VM)描述了肿瘤细胞在无内皮细胞参与下形成新的微循环模式的过程。临床上,VM与侵袭性表型和较差的患者生存率有关。以前的许多研究都集中在血管生成因子方面;最近的研究发现,肿瘤细胞周围的细胞外基质对肿瘤发展具有显著调控作用。细胞外基质蛋白质可能授予肿瘤细胞形成血管生成拟态的能力。在本研究中,我们研究了层黏连蛋白(laminin,LN)基质在黑色素瘤和骨肉瘤的肿瘤进程和VM形成中的作用。相较于Control组,高浓度LN基质培养下,肿瘤细胞的黏附、增殖、迁移、干性表达和VM形成能力显著增强;利用免疫荧光染色和实时定量PCR分析其内在的分子机制,结果显示:与对照组相比,层黏连蛋白基质可以显著促进肿瘤细胞CD133的表达,同时E-钙黏着蛋白I的mRNA表达下调(P<0.05),而Integrin、N-cadherin、Vimentin以及Snail、Twist的mRNA表达上调(P<0.05)。以上研究结果表明,层黏连蛋白促进肿瘤细胞的黏附、增殖、迁移和VM形成能力,并揭示了VM形成的潜在机制,为后期抗血管生成拟态的诊疗提供了新的思路。
Vasculogenic mimicry(VM)refers the process by which tumor cells form new microcirculation patterns in the absence of endothelial cells.Clinically,VM is associated with an aggressive phenotype and poorer patient survival.Many previous studies have focused on angiogenic factors.Recently,more and more studies have found that the extracellular matrix around tumor cells plays a significant role during tumorigensis.Extracellular matrix proteins may render tumor cells to form vasculogenic mimicry.In this study,we investigated the role of laminin(LN)matrix in tumor progression and VM formation in melanoma and osteosarcoma.Compared with the control group,the adhesion,proliferation,migration,stemness expression and VM formation ability of cancer cells were significantly enhanced under high concentrations of LN substrate culture.Immunofluorescence staining and real-time quantitative PCR were used to analyze the internal molecular mechanism.The results showed that compared with the control group,the laminin matrix significantly promoted the expression of CD133 in tumor cells,and the mRNA expression of E-cadherin is down-regulated(P<0.05),while the mRNA expression of Integrin,N-cadherin,Vimentin,Snail and Twist is up-regulated(P<0.05).These results indicate that laminin promotes the adhesion,proliferation,migration and VM formation of tumor cells,and reveals the potential mechanism of VM formation,providing a new idea for the VM diagnosis and treatment.
作者
帅旗志
祖拉莱﹒阿力比衣提
程静雯
王晓婉
梁宇翔
彭志伟
解军
SHUAI Qi-Zhi;ZULALA Halbi-Yat;CHENG Jing-Wen;WANG Xiao-Wan;LIANG Yu-Xiang;PENG Zhi-Wei;XIE Jun(Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,Taiyuan 030001,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第1期63-71,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.82203221)
国家重点研发计划(No.2021YFC2301603)
中央引导地方科技发展资金项目(No.YDZJSX2021B008)
山西省基础研究计划(No.202103021223227)。
关键词
血管生成拟态
层黏连蛋白
细胞外基质
肿瘤微环境
上皮间质转化
vasculogenic mimicry(VM)
laminin
extracellular matrix(ECM)
tumor microenvironment(TME)
epithelial-mesenchymal transition(EMT)
