A framework for advancing our understanding of cancer-associated fibroblasts

Abstract

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment. Extracellular matrix (ECM).The structural network of secreted proteins and glycosaminoglycans that provides structure to tissue. Angiogenesis The formation of new blood vessels. Mesenchyme A type of tissue composed of loosely associated cells surrounded by extracellular matrix. Mesoderm one of three fundamental layers of tissue formed early in development and the predominant source of fibroblastic lineages.

PYCR1-dependent proline synthesis in cancer-associated fibroblasts is required for the deposition of pro-tumorigenic extracellular matrix

“…In conclusion, we have identified PDC as a novel potent epigenetic regulator of collagen-rich ECM production and pinpointed proline metabolism as a critical link between the epigenetic regulation of collagen gene expression and protein production. So far, most of the efforts to reduce ECM production in tumours have focused on targeting pathways that are well known to trigger CAF activation 75…”

Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals conservation of bone microenvironment signatures

“…The role of microenvironment upon cancer formation, and progression to metastasis is supported by numerous studies [19,20], however the current knowledge is not sufficient to reconstruct the chain events from primary to secondary tumor progression. Normal stroma microenvironment is considered to halt tumor formation, however after interaction with tumor cells, it also undergoes a certain "transformation" at the transcriptomic and even at the genetic level [21][22][23][24].…”

The Epigenetic Profile of Tumor Endothelial Cells. Effects of Combined Therapy with Antiangiogenic and Epigenetic Drugs on Cancer Progression

“…The understanding of CAFs biology and potential targeting strategies directed to CAFs constitute a relatively new and highly dynamic field of investigation. Recent excellent reviews summarize the state-of-the-art in this expanding field that will not be discussed further in this review [13,14].Here, we provide an overview of the current literature regarding the epigenetic background of TECs biology, as well as recently performed (and ongoing) clinical trials targeting tumors on the bases of combined treatment with antiangiogenic and epigenetic drugs.…”

“…The understanding of CAFs biology and potential targeting strategies directed to CAFs constitute a relatively new and highly dynamic field of investigation. Recent excellent reviews summarize the state-of-the-art in this expanding field that will not be discussed further in this review [13,14].…”