Scaffold-mediated switching of lymphoma metabolism in culture.

in Cancer & metabolism by Rachana Bhatt, Dashnamoorthy Ravi, Andrew M Evens, Biju Parekkadan

TLDR

  • The study developed a 3D culture model that mimics metabolic patterns of DLBCL in vivo and restraints cell growth.
  • The 3D culture model modulates metabolic pathways similar to clinical specimens, suggesting its potential for personalized therapy and treatment of DLBCL patients.
  • Future research can explore the application of this 3D culture model for predicting treatment outcomes and identifying potential targets for novel anti-cancer therapies.

Abstract

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. 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. 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-Cindicated 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. 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.

Overview

  • The study investigates the metabolism of diffuse large B cell lymphoma (DLBCL) cells in 2D and 3D cell cultures.
  • The study aims to develop an assay platform that replicates metabolic patterns of DLBCL in vivo.
  • The primary objective of the study is to understand metabolic switching in DLBCL cells and its relation to in vivo tumor physiology.

Comparative Analysis & Findings

  • Metabolic profiling and isotope tracer studies revealed metabolic switching in 3D cultures compared to 2D environments.
  • 3D cultures restrained DLBCL cell line growth and modulated metabolic pathways similar to clinical specimens.
  • The study found that 3D matrices can be used to control tumor function towards a slower-growing and metabolically dormant state.

Implications and Future Directions

  • The findings suggest that 3D matrices can be a valuable tool for in vitro modeling of DLBCL and understanding its metabolism.
  • Future studies can explore the application of this 3D culture model for personalized therapy and treatment of DLBCL patients.
  • This research can also be used to identify potential targets for novel anti-cancer therapies and predict treatment outcomes.
Read Full Article