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The regulatory function of SPARC in vascular biology

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Abstract

SPARC is a matricellular protein, able to modulate cell/ECM interactions and influence cell responses to growth factors, and therefore is particularly attuned to contribute to physiological processes involving changes in ECM and cell mobilization. Indeed, the list of biological processes affected by SPARC includes wound healing, tumor progression, bone formation, fibrosis, and angiogenesis. The process of angiogenesis is complex and involves a number of cellular processes such as endothelial cell proliferation, migration, ECM degradation, and synthesis, as well as pericyte recruitment to stabilize nascent vessels. In this review, we will summarize current results that explore the function of SPARC in the regulation of angiogenic events with a particular emphasis on the modulation of growth factor activity by SPARC in the context of blood vessel formation. The primary function of SPARC in angiogenesis remains unclear, as SPARC activity in some circumstances promotes angiogenesis and in others is more consistent with an anti-angiogenic activity. Undoubtedly, the mercurial nature of SPARC belies a redundancy of functional proteins in angiogenesis as well as cell-type-specific activities that alter signal transduction events in response to unique cellular milieus. Nonetheless, the investigation of cellular mechanisms that define functional activities of SPARC continue to contribute novel and exciting paradigms to vascular biology.

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Abbreviations

SPARC:

Secreted protein acidic and rich in cysteine

ECM:

Extracellular matrix

PDGF:

Platelet-derived growth factor

VEGF:

Vascular endothelial growth factor

VEGFR1:

VEGF receptor 1

VEGFR2:

VEGF receptor 2

FGF:

Fibroblast growth factor

TGF-β:

Transforming growth factor-beta

BMP:

Bone morphogenic protein

αSMA:

Alpha smooth muscle actin

ER:

Endoplasmic reticulum

ILK:

Integrin-linked kinase

SHP-1:

Src homology region 2 domain-containing phosphatase-1

CNV:

Choroidal neovascularization

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Acknowledgments

This work was supported in part by the NIH, NCI through R01CA118240 (RAB), NIGMS through T32 GM008203 (LBR), NIDCR through P20RR017696 (ADB), NIHLB through 094517 (ADB), and a Merit Award from the Veteran’s Administration to ADB.

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Authors and Affiliations

  1. Departments of Surgery and Pharmacology and the Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Blvd., NB8.224, Dallas, TX, 75390-8593, USA

    Lee B. Rivera & Rolf A. Brekken

  2. Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, 114 Doughty St., Charleston, SC, 29425, USA

    Amy D. Bradshaw

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  1. Lee B. Rivera
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  2. Amy D. Bradshaw
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  3. Rolf A. Brekken
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Correspondence to Amy D. Bradshaw or Rolf A. Brekken.

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Rivera, L.B., Bradshaw, A.D. & Brekken, R.A. The regulatory function of SPARC in vascular biology. Cell. Mol. Life Sci. 68, 3165–3173 (2011). https://doi.org/10.1007/s00018-011-0781-8

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