Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.
Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.
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DOI：
10.3389/fimmu.2017.01559
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发表时间：
2017
影响因子：
7.3
通讯作者：
Bulla R
中科院分区：
文献类型：
--
作者：
Agostinis C;Vidergar R;Belmonte B;Mangogna A;Amadio L;Geri P;Borelli V;Zanconati F;Tedesco F;Confalonieri M;Tripodo C;Kishore U;Bulla R
C1 q是补体经典途径的第一个识别子组分，其作用于病原体和凋亡细胞的清除。C1 q还已知调节免疫和非免疫细胞的一系列功能，并已被证明参与胎盘发育和感觉突触修剪。我们最近发现，C1 q可以促进肿瘤的粘附，迁移和增殖，除了血管生成和转移。在这项研究中，我们研究了人类C1 q在恶性胸膜间皮瘤（MPM）微环境中的作用，MPM是一种罕见的癌症，通常与接触石棉有关。我们发现C1 q在所有的MPM组织型中高度表达，特别是在上皮样而不是肉瘤样组织型中。C1 q通过其球状结构域与高分子量和低分子量透明质酸（HA）结合。C1 q结合HA能够通过增强ERK 1/2、SAPK/JNK和p38磷酸化来诱导间皮瘤细胞（MES）的粘附和增殖;然而，它不激活补体级联。与球状域的模块化组织一致，我们证明了C1 q可以通过ghA模块与HA结合，而它可以通过ghC与人MES相互作用。总之，在MPM中高表达的C1 q与HA结合并增强肿瘤生长促进细胞粘附和增殖。这些数据可以帮助开发新的诊断标记物和MPM的分子靶点。
C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.
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影响因子：
3.7
作者：
Hong Q;Sze CI;Lin SR;Lee MH;He RY;Schultz L;Chang JY;Chen SJ;Boackle RJ;Hsu LJ;Chang NS
通讯作者：
Chang NS
DOI：
10.1016/j.jtho.2016.04.028
发表时间：
2016-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1311968111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Bossi, Fleur;Tripodo, Claudio;Tedesco, Francesco
通讯作者：
Tedesco, Francesco
影响因子：
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作者：
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