Metabolism shapes the tumor microenvironment

Abstract

Tumors are strongly influenced by the surrounding normal tissue, which forms a specialized niche termed the tumor microenvironment (TME). The TME is modeled by cancer cells for their own benefit through a complex array of interactions. The identification of new forms of communication within the TME, which are dependent on the tumor’s metabolic activity, has expanded our understanding of this heterocellular regulation and has revealed potential therapeutic targets. This review will summarize recent findings on the metabolic regulation of tumor cells by the TME. The concepts to be discussed include the existence of metabolic intratumoral heterogeneity, the contribution of cancer associated fibroblasts (CAFs) to tumor progression, and the regulation of tumor immunology by tumor-secreted metabolites.

Missed Druggable Cancer Hallmark: Cancer–Stroma Symbiotic Crosstalk as Paradigm and Hypothesis for Cancer Therapy

“…A tumor can change its microenvironment, and the microenvironment can affect how a tumor grows and spreads.” In solid tumors, the cancer microenvironment consists of two main components, cellular and non‐cellular, whose proportion and composition vary depending on the location and stage of the tumor. The non‐cellular components mainly include the extracellular matrix (ECM), composed of proteins, glycoproteins, and proteoglycans, serving as a scaffold that supports tissue architecture . The cellular components include fibroblasts, such as cancer associated fibroblasts (CAFs), mesenchymal stem cells, adipocytes, pericytes, endothelial cells, networks of lymphatic vessels, and tumor‐infiltrating cells of the immune system .…”

“…One of the most significant features of CAFs is that their phenotype, that is, promoting tumor progression, is stably maintained in vitro and ex vivo even without steady contact with neighboring cancer cells . Recent studies report that many types of cells may be recruited as predecessors of CAFs: resident tissue fibroblasts, peritumoral adipocytes, bone marrow mesenchymal stem cells, hematopoietic stem cells, and many others .…”

“…The non-cellular components mainly include the extracellular matrix (ECM), composed of proteins, glycoproteins, and proteoglycans, serving as a scaffold that supports tissue architecture. [4,11,26] The cellular components include fibroblasts, such as cancer associated fibroblasts (CAFs), mesenchymal stem cells, adipocytes, pericytes, endothelial cells, networks of lymphatic vessels, and tumor-infiltrating cells of the immune system. [21,[27][28][29][30] From the therapeutic point of view, immune cell interactions with cancer cells might be the most successful targets for cancer treatment, and they could serve as a paradigm for a more general approach.…”

“…[77,85] One of the most significant features of CAFs is that their phenotype, that is, promoting tumor progression, is stably maintained in vitro and ex vivo even without steady contact with neighboring cancer cells. [26,78,86] Recent studies report that many types of cells may be recruited as predecessors of CAFs: resident tissue fibroblasts, peritumoral adipocytes, bone marrow mesenchymal stem cells, hematopoietic stem cells, and many others. [78,81] After being recruited from various sources, a subset of these precursors acquires the CAF phenotype through www.advancedsciencenews.com www.bioessays-journal.com complex activation processes that are still poorly understood.…”

Metabolic landscape of the tumor microenvironment

“…In addition to the unique metabolic demands of each cell type, each cancer experiences a distinct nutrient environment, distinct engagement of extracellular signals, and may derive from a different cell of origin thus possibly having distinct mutational patterns 9 . Therefore at the cellular level, each cell within the tumor is likely to have a different metabolic status [10][11][12] . Nevertheless, direct observations of cellular metabolism in vivo at the level of single cells is difficult.…”