Modeling Cell Communication in Cancer With Organoids: Making the Complex Simple

Abstract

Homotypic and heterotypic interactions between cells are of crucial importance in multicellular organisms for the maintenance of physiological functions. Accordingly, changes in cell-to-cell communication contribute significantly to tumor development. Cancer cells engage the different components of the tumor microenvironment (TME) to support malignant proliferation, escape immune control, and favor metastatic spreading. The interaction between cancerous and non-cancerous cell types within tumors occurs in many ways, including physical contact and paracrine signaling. Furthermore, local and long-range transfer of biologically active molecules (e.g., DNA, RNA, and proteins) can be mediated by small extracellular vesicles (EVs) and this has been shown to influence many aspects of tumor progression. As it stands, there is a critical need for suitable experimental systems that enable modeling the cell-to-cell communications occurring in cancer. Given their intrinsic complexity, animal models represent the ideal system to study cell-to-cell interaction between different cell types; however, they might make difficult to assess individual contribution to a given phenotype. On the other hand, simplest experimental models (i.e., in vitro culture systems) might be of great use when weighing individual contributions to a given phenomenon, yet it is imperative that they share a considerable number of features with human cancer. Of the many culture systems available to the scientific community, patient-derived organoids already proved to faithfully recapitulate many of the traits of patients' disease, including genetic heterogeneity and response to therapy. The organoid technology offers several advantages over conventional monolayer cell cultures, including the preservation of the topology of cell-to-cell and cell-to-matrix interactions as observed in vivo. Several studies have shown that organoid cultures can be successfully used to study interaction between cancer cells and cellular components of the TME. Here, we discuss the potential of using organoids to model the interplay between cancer and non-cancer cells in order to unveil biological mechanisms involved in cancers initiation and progression, which might ultimately lead to the identification of novel intervention strategy for those diseases.

Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment

“…Based on this evidence, a precise definition of BC organoids media components is required to better preserve parental tumor features. Developing organoids together with native or reconstituted stromal components might also be a strategy to supply the organoids with specific tumor niche factors [ 30 ].…”

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

“…Moreover, the presence of tumor vesicles in the tissues of patients can be considered as biomarkers of cancer. The identification of vesicle proteins in the medium after tumor organoids cultivation may become a new approach for the detection of biomarkers [ 75 ]. The investigation of biomarkers can also be carried out by comparing the transcriptional differences between the lines of healthy and tumor organoids [ 87 ].…”

COVID-19–Induced Modifications in the Tumor Microenvironment: Do They Affect Cancer Reawakening and Metastatic Relapse?

“…Recent studies on protein-protein interactions during COVID-19 revealed that common cancer pathways were targeted by SARS-CoV-2, including those involved in cell cycle progression, metabolism and epigenetics (86). However, the interactions between SARS-CoV-2, cancer cells and the immune system are currently unknown and will need to be investigated in detail, possibly with the use of complex in vitro models that reproduce multicellular microenvironments (87). By contrast, in vivo studies to explore COVID-19 and cancer recurrence would likely be challenging, as they should employ mice with multiple genetic modifications predisposing to both COVID-19 and cancer (such as mice transgenic for hACE2 and ErbB2/Neu).…”