Co‐culturing multicellular tumor models: Modeling the tumor microenvironment and analysis techniques

Abstract

Advances in two-dimensional (2D) and three-dimensional (3D) cell culture over the last 10 years have led to the development of a plethora of methods for cultivating tumor models. More recently, cellular co-cultures have become a suitable testbed. The first portion of this review focuses on co-culturing methods that have been developed in recent years utilizing the multicellular tumor spheroid model. The latter portion describes techniques that are used to analyze the proteomes of mono-or co-cultured tumor models, with a focus on mass spectrometry (MS)-based analyses. Protein profiles are important indicators of the tumor heterogeneity. Therefore, there is a specific focus within this review on analysis by MS and MS imaging methods evaluating the proteomic profiles of 2D and 3D co-cultures. While these models are incredibly important for biological research, so far, they have not been widely explored on the proteomic level. With this review, we aim to introduce these systems to an analytical audience, with the goal of highlighting MS as an underutilized tool for proteomic analysis of tumor models.

Lipidomic comparison of 2D and 3D colon cancer cell culture models

“…Co‐culturing cells have increasingly been recognized as a technique to understand cell‐to‐cell communication and to better model the tumor microenvironment 13 . Gong et al investigated the role of cancer‐associated fibroblasts in modifying the lipidome after co‐culturing with DLD‐1 cells.…”

“…12 Co-culturing cells have increasingly been recognized as a technique to understand cell-to-cell communication and to better model the tumor microenvironment. 13 Gong et al investigated the role of cancer-associated fibroblasts in modifying the lipidome after coculturing with DLD-1 cells. This study suggests that lipidomic reprogramming and increased tumor metastasis is due to lipid metabolite crosstalk between cell types.…”

Three-Dimensional Mass Spectrometry Imaging Reveals Distributions of Lipids and the Drug Metabolite Associated with the Enhanced Growth of Colon Cancer Cell Spheroids Treated with Triclosan

“…In order to investigate the distribution of these compounds in tumor tissues, traditional imaging methods such as PET, MRI, and fluorescence imaging (FI) have been used, which either have a low spatial resolution (millimeter level, for example, PET and MRT) or need a time-consuming labeling procedure (e.g., FI) . MALDI-MSI is a label-free imaging technology that provides a better spatial resolution for cancer research . Therefore, MALDI MSI was employed to map the distribution of TCSS in HCT116 CCS exposed to TCS (10 μM) at different time points.…”

“… 22 MALDI-MSI is a label-free imaging technology that provides a better spatial resolution for cancer research. 23 Therefore, MALDI MSI was employed to map the distribution of TCSS in HCT116 CCS exposed to TCS (10 μM) at different time points. Each time point contained three cell spheroids.…”

Models for Translational Proton Radiobiology—From Bench to Bedside and Back

“…Organoids can also be grown from mouse tissue, which opens a wide range of possibilities for biological studies, including the use of transgenic donors [126,127]. However, some research questions call for even higher complexity mirrored by the co-culturing of multicellular spheroids or organoids with various stromal cell types, such as fibroblasts, endothelial, or hematopoietic cells [128][129][130][131].…”