Abstract
Metabolism is considered to be the core of all cellular activity. Thus, extensive studies of metabolic processes are ongoing in various fields of biology, including cancer research. Cancer cells are known to adapt their metabolism to sustain high proliferation rates and survive in unfavorable environments with low oxygen and nutrient concentrations. Hence, targeting cancer cell metabolism is a promising therapeutic strategy in cancer research. However, cancers consist not only of genetically altered tumor cells but are interwoven with endothelial cells, immune cells and fibroblasts, which together with the extracellular matrix (ECM) constitute the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are linked to poor prognosis in different cancer types, are one important component of the TME. CAFs play a significant role in reprogramming the metabolic landscape of tumor cells, but how, and in what manner, this interaction takes place remains rather unclear. This review aims to highlight the metabolic landscape of tumor cells and CAFs, including their recently identified subtypes, in different tumor types. In addition, we discuss various in vitro and in vivo metabolic techniques as well as different in silico computational tools that can be used to identify and characterize CAF–tumor cell interactions. Finally, we provide our view on how mapping the complex metabolic networks of stromal-tumor metabolism will help in finding novel metabolic targets for cancer treatment.
Highlights
We present the idea of mapping the complex metabolic landscape of tumor cells and Cancer-associated fibroblasts (CAFs) in order to reach mechanistic insights, by the integration of multi-omics data into context-specific metabolic models
Human proteins are composed by 20 different proteinogenic amino acids, which are divided into two different groups: the essential amino acids (EAAs: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine) and the nonessential amino acids (NEAAs: alanine, aspartate, asparagine, arginine, cysteine, glutamate, glutamine, glycine, proline, serine and tyrosine) [58]
CAFs can limit the anti-tumor immunity by either reducing immune cell infiltration or increasing an immunosuppressive state, or a combination of both. These interactions are suggested to impair the response to current immunotherapies in different cancer types
Summary
Max Borst first noted the importance of the tumor microenvironment (TME) on cancer progression in 1902 [1]. CAFs are fibroblasts that display an activated phenotype: they tend to be larger than their normal counterparts, are spindle-shaped and show the presence of stress fibers. CAFs seem to be constantly activated and unable to revert to a quiescent phenotype [2] This observation contributed to Harold Dvorak’s definition of cancer as “the wound that does not heal” [3]. CAFs communicate with cancer cells in various ways in supporting tumorigenesis These include signaling molecules, secretion of growth factors, interleukins and metabolite exchanges [5]. CAFs secrete pro-angiogenic factors like vascular endothelial factor (VEGF) and endothelial growth factor (EGF) Most of these factors display pro-tumorigenic effects leading to disease progression. We discuss the future development of therapeutic strategies considering metabolic targets identified in CAFs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
