Collaboration to measure metabolism of 3D microtissue

The US-based Seahorse Bioscience and Moffitt Cancer Center have received an SBIR contract, through the National Cancer Institute, to develop a reproducible method that will enable the measurement of metabolism of 3D microtissue. The method will be used for high-throughput metabolic and preclinical toxicity screens.

Cancer cells switch their metabolic pathways to survive, so the ability to perform real-time measurements of the metabolism of tumours will provide important information in developing anticancer drugs. The work will focus on the testing of non-small cell lung cancers (NSCLC) to investigate response to both targeted and non-targeted chemotherapeutic agents. The goal of the study is to develop the feasibility data to quantitatively assess the metabolic effects of various treatments on NSCLC, with an ultimate aim of advancing personalised cancer treatment.

The work will involve both optimised 3D cell cultures (spheroids) of cancer cells and cancer tissue procured via biopsy. Optimisation will establish standard processing protocols to yield consistent microtissue samples and then measure the metabolic signatures of the samples in response to therapeutic treatments. 3D cell cultures that contain multiple cell types provide a more physiologically relevant model for in vitro assays than traditional 2D cell cultures, with the potential for better predictability of in vivo outcomes.

The research will be done using the Seahorse XF^e96 Extracellular Flux Analyzer and novel XF^e96 Spheroid Microplates, which provide functional metabolic measurements from 3D spheroids. Andrew Neilson, chief technical officer for Seahorse Bioscience, “Seahorse XF technology is proven for the measurement of metabolism in pancreatic islets; now we’re applying our knowledge to measuring spheroid metabolism.

“XF 3D metabolic assays have the potential to impact cancer research as we enable scientists to analyse a more in vivo model of cancer metabolism,” Neilson said. “These methods should allow us to evaluate the efficacy of a wide range of treatments using 3D microtissues. These XF assays can be applied to most tumour cell lines, enabling scientists to probe drug effects on metabolic pathways and develop personalised therapies tailored to the tumour characteristics.”

“This is a very exciting opportunity because we know that the metabolism of intact cancer tissue is complex and involves cross-talk between the cancer cells and the supporting host cells,” said Dr Robert J Gillies, vice-chair of radiology and director of Moffitt’s experimental imaging program. “This metabolic syncytium is necessary for cancers to thrive, and itself presents opportunities for novel therapies that could not be assessed in monoculture. Also, we fully expect that the response of these complex tissues to current and novel therapeutics will be highly predictive of their behaviour in a patient.”

The method, if successful, will be compatible with most tumour cell lines and will have the capability for co-culture with human primary cells. The long-term goal is to move into translational medicine, developing ways to characterise tumours using small tissue biopsies. Additionally, applications for XF 3D microtissue assay technology will extend beyond cancer to also include diabetes, obesity, toxicology, stem cell therapy and neurodegeneration research.