The use of a multi-metric readout screen to identify EHMT2/G9a-inhibition as a modulator of cancer-associated fibroblast activation state.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression, including mediating tumour cell invasion via their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM). Given that reduced CAF abundance in tumours correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in regions of tumour-stromal mixing with the goal of reducing tumour aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) platform, we performed an image-based, phenotypic screen that enabled us to identify modulators of CAF abundance and the capacity of CAFs to induce tumour cell invasion.

Single-Cell Analysis Reveals Transcriptomic Features of Drug-Tolerant Persisters and Stromal Adaptation in a Patient-Derived EGFR-Mutated Lung Adenocarcinoma Xenograft Model.

Introduction: Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is mainly driven by minor subpopulations of drug-tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted with cell line models.

Guided Self-Assembly of ES-Derived Lung Progenitors into Biomimetic Tube Structures That Impact Cell Differentiation.

Chemically directed differentiation of pluripotent stem cells (PSCs) into defined cell types is a potent strategy for creating regenerative tissue models and cell therapies. In vitro observations suggest that physical cues can augment directed differentiation. We recently demonstrated that confining human PSC-derived lung progenitor cells in a tube with a diameter that mimics those observed during lung development results in the alteration of cell differentiation towards SOX2SOX9 lung cells.

Patient-derived cell line, xenograft and organoid models in lung cancer therapy.

Lung cancer accounts for most cancer-related deaths worldwide and has an overall 5-year survival rate of ~15%. Cell lines have played important roles in the study of cancer biology and potential therapeutic targets, as well as pre-clinical testing of novel drugs. However, most experimental therapies that have cleared preclinical testing using established cell lines have failed phase III clinical trials.

Assembly of lung progenitors into developmentally-inspired geometry drives differentiation via cellular tension.

During organogenesis groups of differentiating cells self-organize into a series of structural intermediates with defined architectural forms. Evidence is emerging that such architectural forms are important in guiding cell fate, yet in vitro methods to guide cell fate have focused primarily on un-patterned exposure of stems cells to developmentally relevant chemical cues. We set out to ask if organizing differentiating lung progenitors into developmentally relevant structures could be used to influence differentiation status.

Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A tissue model to probe tumour phenotypes at tumour-stroma interfaces.

The interface between a tumour and the adjacent stroma is a site of great importance for tumour development. At this site, carcinoma cells are highly proliferative, undergo invasive phenotypic changes, and directly interact with surrounding stromal cells, such as cancer-associated fibroblasts (CAFs) which further exert pro-tumorigenic effects. Here we describe the development of GLAnCE (Gels for Live Analysis of Compartmentalized Environments), an easy-to-use hydrogel-culture platform for investigating CAF-tumour cell interaction dynamics in vitro at a tumour-stroma interface.

A TRACER 3D Co-Culture tumour model for head and neck cancer.

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours. TRACER culture involves infiltrating cells into a thin fibrous scaffold and then rolling the resulting biocomposite around a mandrel to generate a 3D and layered structure.

The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted.

Modulation of cellular polarization and migration by ephrin/Eph signal-mediated boundary formation.

Compartment boundaries are essential for ensuring proper cell organization during embryo development and in adult tissues, yet the mechanisms underlying boundary establishment are not completely understood. A number of mechanisms, including (i) differential adhesion, (ii) differential tension, and (iii) cell signaling-mediated cell repulsion, are known to contribute and likely a context-dependent balance of each of these dictates boundary implementation. The ephrin/Eph signaling pathway is known to impact boundary formation in higher animals.

Correction: Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration.

Correction for 'Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration' by Michael Woolman et al., Analyst, 2017, 142, 3250-3260.

Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration.

Squamous cell carcinomas constitute a major class of head & neck cancers, where the tumour stroma ratio (TSR) carries prognostic information. Patients affected by stroma-rich tumours exhibit a poor prognosis and a higher chance of relapse. As such, there is a need for a technology platform that allows rapid determination of the tumour stroma ratio.

An in vitro model of tissue boundary formation for dissecting the contribution of different boundary forming mechanisms.

During development and in adult tissues separation of phenotypically distinct cell populations is necessary to ensure proper organization and function of tissues and organs. Various phenomena, such as differential adhesion, differential mechanical tension and cell-cell repulsion, are proposed to cause boundary formation. Moreover, emerging evidence suggests that interplay between multiple such phenomena can underlie boundary formation.

Micropatterning strategies to engineer controlled cell and tissue architecture in vitro.

Micropatterning strategies, which enable control over cell and tissue architecture in vitro, have emerged as powerful platforms for modelling tissue microenvironments at different scales and complexities. Here, we provide an overview of popular micropatterning techniques, along with detailed descriptions, to guide new users through the decision making process of which micropatterning procedure to use, and how to best obtain desired tissue patterns. Example techniques and the types of biological observations that can be made are provided from the literature.