The role of chemokine ligands and receptors in the dissemination of anaplastic large cell lymphoma

趋化因子配体和受体在间变性大细胞淋巴瘤传播中的作用

• 批准号: 344458846
• 负责人: Professorin Dr. Sylvia Hartmann
• 金额: --
• 依托单位: Dr. Senckenbergisches Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/344458846?language=en
• 关键词: role; chemokine; ligands; receptors; dissemination

Anaplastic large cell lymphoma (ALCL) is a CD30-expressing T-cell lymphoma, showing morphologic overlap with Hodgkin lymphoma (HL). However, important differences in clinical behavior have been observed: ALCL usually presents with advanced stage and has a worse prognosis. Whereas in HL the cellular microenvironment as well as the chemokines and their corresponding receptors, which together contribute to the composition of the microenvironment, have been extensively studied, very little is known about the microenvironment and the expression of chemokines and their receptors in ALCL. Chemokines and their receptors crucially impact the distribution and trafficking of leukocytes. Therefore, the aim of the present study is to characterize chemokine ligand and receptor expression on tumor and bystander cells in ALCL and to characterize the composition of the microenvironment in primary ALCL samples in order to better understand the microenvironmental niche which provides survival advantage for ALCL tumor cells. The findings in primary ALCL specimens can then be applied on in vitro experiments and experiments in native human lymphoid tissue with ALCL cell lines. Chemokine receptor expression will be modulated in ALCL cell lines and behavior of the ALCL tumor cells will be monitored in coculture with reactive bystander cells as well as in migration assay chamber experiments. Furthermore, GFP-labeled ALCL cell lines with and without expression of certain chemokine receptors will be applied onto primary thick slides of human lymphoid tissue. With this assay, additionally reactive bystander cells can be highlighted and the reactions, movements and interactions of all labeled cells will be visualized using live cell imaging. These experiments shall lead to a better understanding of the migration behavior and the distribution of ALCL tumor cells in human lymphoid tissue as well as their interaction with the cellular microenvironment. Differences in the microenvironmental interactions and chemokine expression may give an explanation of the differing clinical behavior when compared with cHL. Furthermore, the effects of novel therapeutic approaches in ALCL can be tested in primary human tissue under visual monitoring.

间变性大细胞淋巴瘤（ALCL）是一种表达CD30的T细胞淋巴瘤，与霍奇金淋巴瘤（HL）有形态学重叠。然而，已经观察到临床行为的重要差异：ALCL通常表现为晚期，预后较差。然而，在HL中，细胞微环境以及趋化因子及其相应的受体（它们共同构成了微环境的组成）已被广泛研究，但对ALCL中的微环境以及趋化因子及其受体的表达知之甚少。趋化因子及其受体对白细胞的分布和运输有重要影响。因此，本研究的目的是表征ALCL中肿瘤和旁观者细胞上的趋化因子配体和受体表达，并表征原发性ALCL样本中微环境的组成，以便更好地了解为ALCL肿瘤细胞提供生存优势的微环境生态位。原代ALCL标本中的发现可应用于体外实验和ALCL细胞系在天然人淋巴组织中的实验。将在ALCL细胞系中调节趋化因子受体表达，并在与反应性旁观者细胞共培养以及迁移试验室实验中监测ALCL肿瘤细胞的行为。此外，将表达和不表达某些趋化因子受体的GFP标记的ALCL细胞系应用于人淋巴组织的原代厚载玻片上。通过该测定，可以突出显示另外的反应性旁观者细胞，并且使用活细胞成像将所有标记细胞的反应、运动和相互作用可视化。这些实验将有助于更好地了解ALCL肿瘤细胞在人淋巴组织中的迁移行为和分布以及它们与细胞微环境的相互作用。与cHL相比，微环境相互作用和趋化因子表达的差异可能解释了不同的临床行为。此外，ALCL的新治疗方法的效果可以在视觉监测下在原代人体组织中进行测试。