Metabolic Relationship between Cancer-Associated Fibroblasts and Cancer Cells

  • Christos Sazeides
  • Anne LeEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1063)


Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in cancer initiation, progression, and metastasis. Recent findings have demonstrated that the TME not only provides physical support for cancer cells, but also directs cell-to-cell interactions (in this case the interaction between cancer cells and CAFs). As cancer progresses, the CAFs also co evolve—transitioning from an inactivated state to an activated state. The elucidation and understanding of the interaction between cancer cells and CAFs will pave the way for new cancer therapies [1–3].

The TME is a heterogeneous environment consisting of fibroblasts, tumor-associated macrophages, adipocytes, an extracellular matrix, and mesenchymal stem cells [4]. The exact composition of each stroma varies depending on cancer and tissue type. To add to this variation, there is heterogeneity even within the CAF population itself. Different CAFs express different markers and influence stromal pro-tumorigenic capacity and cancer progression in diverse ways [5, 6].


Cancer-associated fibroblasts CAF-derived exosomes Glutamine metabolism Hypoxia-inducible factor-1 Reverse Warburg effect 



α-Smooth muscle actin


Cancer-associated fibroblast


Caveolin -1


CAF-derived exosomes


Epithelial-mesenchymal transition


Fatty acid synthase




Hypoxia-inducible factor-1


Lactate dehydrogenase A


Monocarboxylate transporter


Normal fibroblasts


Pancreatic ductal adenocarcinoma


Pyruvate kinase isozymes M1/M2


Pancreatic stellate cells


Reactive oxygen species


Succinate dehydrogenase


Tricarboxylic acid


Transforming growth factor beta


Tumor microenvironment


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center for Cellular ImmunotherapiesUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  2. 2.Department of Pathology and OncologyJohns Hopkins University School of MedicineBaltimoreUSA

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