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Versican: Role in Cancer Tumorigenesis

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Extracellular Matrix in Tumor Biology

Part of the book series: Biology of Extracellular Matrix ((BEM))

Abstract

Versican is an extracellular matrix proteoglycan that is expressed in a wide variety of cancers. Several cellular sources for versican have been identified in a multitude of cancers including tumor cells, stromal cells, myeloid cells, and lymphoid cells. Versican plays a role in five of the six hallmarks of cancer including proliferative signaling, evasion of growth suppressor signaling, promotion of tissue invasion and metastasis, angiogenesis, and resistance to cell death. Versican also interacts with growth factors and cytokines to modify their activity and involvement in the cancer response. The synthesis and accumulation of versican is regulated by similar pathways that regulate cancer progression, such as the canonical Wnt/β-catenin pathway and receptor tyrosine kinases. The expression and accumulation of versican are associated with poor prognosis, disease progression, metastasis, and chemoresistance. A detailed analysis of the role of versican in the disease course of leiomyosarcoma is provided here as an example of the importance of this extracellular matrix component in cancer pathogenesis. Collectively, our results and those from other groups suggest that versican could serve as a point of control in the management and treatment of many cancers.

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Abbreviations

ADAMTS:

A disintegrin and metalloproteinase with a thrombospondin family

CAF:

Cancer-associated fibroblast

CTLs:

Cytotoxic T lymphocytes

DAMP:

Danger-associated molecular pattern

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

FAK:

Focal adhesion kinase

α-GAG:

α-Glycosaminoglycan

β-GAG:

β-Glycosaminoglycan

HAS:

Hyaluronan synthase

HYAL1:

Hyaluronidase-1

LEFs:

Lymphoid-enhancing factors

LMS:

Leiomyosarcoma

LOX:

Lysyl oxidase

MMP:

Matrix metalloproteinase

PSCs:

Pancreatic stellate cells

PSGL-1:

P-selectin glycoprotein ligand-1

RHAMM:

Hyaluronan-mediated motility receptor

αSMA+ :

Alpha smooth muscle actin positive

TAMs:

Tumor-associated macrophages

TCFs:

T-cell factors

TGFβ:

Transforming growth factor beta

TLR2:

Toll-like receptor 2

TNFα:

Tumor necrosis factor α

TSP1:

Thrombospondin-1

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Acknowledgments

We acknowledge Pioneer Award funding from the Wilske Center for Translational Research at Virginia Mason Medical Center and the Benaroya Research Institute. Dr. Kang was supported by the Ann Ramsay-Jenkins and William M. Jenkins Fellowship for Matrix Biology. We thank Dr. Virginia M. Green for the careful editing and preparation of this manuscript.

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  1. Matrix Biology Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA, 98101, USA

    Paul A. Keire, Inkyung Kang & Thomas N. Wight

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  1. Paul A. Keire
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  2. Inkyung Kang
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Correspondence to Thomas N. Wight .

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  1. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center , Dallas, Texas, USA

    Rolf A. Brekken

  2. Department of Reproductive Medicine, University of California , La Jolla, California, USA

    Dwayne Stupack

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Keire, P.A., Kang, I., Wight, T.N. (2017). Versican: Role in Cancer Tumorigenesis. In: Brekken, R., Stupack, D. (eds) Extracellular Matrix in Tumor Biology. Biology of Extracellular Matrix. Springer, Cham. https://doi.org/10.1007/978-3-319-60907-2_4

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