As a result of elevated metabolic rates and net acid extrusion in the rapidly proliferating cancer cells, solid tumours are characterized by a highly acidic microenvironment, while cancer cell intracellular pH is normal or even alkaline. Two-dimensional (2D) cell monocultures, which have been used extensively in breast cancer research for decades, cannot precisely recapitulate the rich environment and complex processes occurring in tumours in vivo. The use of such models can consequently be misleading or non-predictive for clinical applications. Models mimicking the tumour microenvironment are particularly pivotal for studying tumour pH homeostasis, which is profoundly affected by the diffusion-limited conditions in the tumour. To advance the understanding of the mechanisms and consequences of dysregulated acid–base homeostasis in breast cancer, clinically relevant models that incorporate the unique microenvironment of these tumours are required. The development of three-dimensional (3D) cell cultures has provided new tools for basic research and pre-clinical approaches, allowing the culture of breast cancer cells under conditions that closely resemble tumour growth in a living organism. Here we provide an overview of the main 3D techniques relevant for breast cancer cell culture. We discuss the advantages and limitations of the classical 3D models as well as recent advances in 3D culture techniques, focusing on how these culture methods have been used to study acid–base transport in breast cancer. Finally, we outline future directions of 3D culture technology and their relevance for studies of acid–base transport.
-
Cover Image
Cover Image
The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. In this issue Klausen and colleagues (1733–1748) provide an overview about the optogenetic tools and biosensors used to explore the subcellular organization of cAMP signalling. The cover image depicts time projection (colour represents time) of a head-tethered transgenic mouse sperm expressing the photo-activated adenylate cyclase bPAC. Image courtesy of Dagmar Wachten.
3D multicellular models to study the regulation and roles of acid–base transporters in breast cancer
Dominika Czaplinska, Line O. Elingaard-Larsen, Michala G. Rolver, Marc Severin, Stine F. Pedersen; 3D multicellular models to study the regulation and roles of acid–base transporters in breast cancer. Biochem Soc Trans 20 December 2019; 47 (6): 1689–1700. doi: https://doi.org/10.1042/BST20190131
Download citation file:
Sign in
Sign in to your personal account
Captcha Validation Error. Please try again.