Scaffold-mediated switching of lymphoma metabolism in culture.

IF 6 3区医学 Q1 CELL BIOLOGY

Cancer & Metabolism Pub Date : 2022-10-12 DOI:10.1186/s40170-022-00291-y

Rachana Bhatt, Dashnamoorthy Ravi, Andrew M Evens, Biju Parekkadan

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Abstract

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and accounts for about a third of all NHL cases. A significant proportion (~40%) of treated DLBCL patients develop refractory or relapsed disease due to drug resistance which can be attributed to metabolomic and genetic variations amongst diverse DLBCL subtypes. An assay platform that reproduces metabolic patterns of DLBCL in vivo could serve as a useful model for DLBCL.

Methods: This report investigated metabolic functions in 2D and 3D cell cultures using parental and drug-resistant DLBCL cell lines as compared to patient biopsy tissue.

Results: A 3D culture model controlled the proliferation of parental and drug-resistant DLBCL cell lines, SUDHL-10, SUDHL-10 RR (rituximab resistant), and SUDHL-10 OR (obinutuzumab resistant), as well as retained differential sensitivity to CHOP. The results from metabolic profiling and isotope tracer studies with D-glucose-¹³C₆ indicated metabolic switching in 3D culture when compared with a 2D environment. Analysis of DLBCL patient tumor tissue revealed that the metabolic changes in 3D grown cells were shifted towards that of clinical specimens.

Conclusion: 3D culture restrained DLBCL cell line growth and modulated metabolic pathways that trend towards the biological characteristics of patient tumors. Counter-intuitively, this research thereby contends that 3D matrices can be a tool to control tumor function towards a slower growing and metabolically dormant state that better reflects in vivo tumor physiology.

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支架介导的淋巴瘤培养新陈代谢转换。

背景：弥漫大B细胞淋巴瘤（DLBCL）是非霍奇金淋巴瘤（NHL）的一种侵袭性亚型，约占所有NHL病例的三分之一。在接受治疗的 DLBCL 患者中，有相当一部分（约 40%）因耐药性而出现难治或复发，这可能是由于不同 DLBCL 亚型之间的代谢组学和基因变异造成的。能再现 DLBCL 体内代谢模式的检测平台可作为 DLBCL 的有用模型：本报告使用亲代和耐药DLBCL细胞系与患者活检组织对比，研究了二维和三维细胞培养物的代谢功能：结果：三维培养模型控制了亲代和耐药 DLBCL 细胞系 SUDHL-10、SUDHL-10 RR（利妥昔单抗耐药）和 SUDHL-10 OR（奥比妥珠单抗耐药）的增殖，并保留了对 CHOP 的不同敏感性。使用 D-glucose-13C6 进行的代谢分析和同位素示踪研究结果表明，与二维环境相比，三维培养中的代谢发生了转换。结论：三维培养抑制了 DLBCL 细胞系的生长，并调节了代谢途径，使其趋向于患者肿瘤的生物学特征。结论：三维培养抑制了 DLBCL 细胞系的生长，并调节了代谢途径，使其趋向于患者肿瘤的生物学特征。与直觉相反，这项研究认为三维基质可以作为一种工具，控制肿瘤功能，使其趋向于生长缓慢、代谢休眠的状态，从而更好地反映体内肿瘤的生理机能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.