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The Multifaceted Role of Cancer Associated Fibroblasts in Tumor Progression

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Tumor-Associated Fibroblasts and their Matrix

Part of the book series: The Tumor Microenvironment ((TTME,volume 4))

Abstract

The fibroblast is a key player in the stroma of epithelial malignancies. Recently relatively specific fibroblast markers have been identified, facilitating the assessment of how fibroblasts and cancer cells interact. While the malignant cells activate fibroblasts in the tumor stroma, cancer associated fibroblasts secrete growth factors and build a permissive soil in which the cancer cells thrive. There is a great controversy in the research community today as to the possible existence of fibroblast mutations in epithelial cancers, which we will discuss. Furthermore, the prognostic role of fibrosis in tumors will be debated, along with future therapeutic strategies targeted at cancer associated fibroblasts.

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Notes

  1. 1.

    The FSP1-GFP mice were a kind gift from E.G. Neilson.

  2. 2.

    FSP1-Cre and R26R-EYFP reporter mice were kindly provided by E.G. Neilson and B. G. Neel respectively.

Abbreviations

αSMA:

α-Smooth muscle actin

bFGF:

Basic fibroblast growth factor

BMH:

Bone marrow-derived hematopoietic precursor cells

BMM:

Bone marrow-derived mesenchymal precursor cells

CAF:

Cancer associated fibroblast

CK5:

Cytokeratin 5

DAB:

3,3¢-diaminobenzidine

ECM:

Extracellular matrix

EMT:

Epithelial-to-mesenchymal transition

EndMT:

Endothelial-to-mesenchymal transition

ER:

Estrogen receptor

FAP:

Fibroblast activation protein

FSP1:

Fibroblast specific protein-1

HGF:

Hepatocyte growth factor

IGF:

Insulin-like growth factor

KGF:

Keratinocyte growth factor

MMP:

Matrix metalloproteinase

MMPI:

Matrix metalloproteinase inhibitor

NG2:

NG2 chondroitin sulfate proteoglycan

PDGF:

Platelet derived growth factor

SCC:

Squamous cell carcinoma

TGFb:

Transforming growth factor-b.

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Acknowledgements

This work was primarily supported by National Institutes of Health Grant DK62987 and partially by National Institutes of Health Grants DK55001, DK61688, AA13913, and CA12550 and funds from the Department of Medicine for the Division of Matrix Biology at Beth Israel Deaconness Medical Center. This work was also supported by the Champalimaud Foundation. HPE was supported by grants from the University of Bergen and the Eckbo Legacy, Norway.

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Authors and Affiliations

  1. Department of Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway

    Hans Petter Eikesdal

  2. Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center & Harvard Medical School, 330 Brookline Ave, E/CLS Room #11-090, Center for Life Sciences, 02115, Boston, MA, USA

    Raghu Kalluri

  3. Department of Oncology, Haukeland University Hospital, 5021, Bergen, Norway

    Hans Petter Eikesdal

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  1. Hans Petter Eikesdal
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Editors and Affiliations

  1. Siederstrasse 13, Villingen-Schwenningen, 78054, Germany

    Margareta M. Mueller

  2. Am Pferchelhang 32, Heidelberg, 69118, Germany

    Norbert E. Fusenig

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Eikesdal, H., Kalluri, R. (2011). The Multifaceted Role of Cancer Associated Fibroblasts in Tumor Progression. In: Mueller, M., Fusenig, N. (eds) Tumor-Associated Fibroblasts and their Matrix. The Tumor Microenvironment, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0659-0_19

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