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SPARC and the Tumor Microenvironment

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Tumor-Associated Fibroblasts and their Matrix

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

Abstract

Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein that modulates the levels of cell adhesion and migration, as well as regulates cell proliferation, survival, and angiogenesis during normal development and tissue remodeling. These same cellular processes are necessary for tumor growth and progression, and they proceed as a result of the interplay between the tumor cells and the stromal and immune cells within the tissue microenvironment. Evidence suggests that SPARC contributes to these tumor-associated processes; however, deciphering its role is complicated by the fact that SPARC may be produced and secreted by cancer cells, stromal cells, and immune cells resulting in autocrine and paracrine effects on the tumor microenvironment. Its ability to promote deadhesion of cells from the ECM results in tumor and stromal cell migration and dissemination. It can also inhibit proliferation in cancer cells, fibroblasts, and endothelial cells directly or indirectly by binding to various growth factors and inhibiting downstream signaling. In addition, SPARC can regulate ECM deposition, assembly, and remodeling by regulating collagen processing and altering the secretion of matrix proteins and matrix degrading proteases from cancer cells and stromal cells. Finally, SPARC can also regulate the tumor microenvironment by suppressing immune cell infiltration and limiting tumor elimination. The evidence for each of these functions of SPARC in the regulation of the tumor microenvironment will be discussed.

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Abbreviations

AML:

acute myeloid leukemia

BAE:

bovine aortic endothelial

bFGF:

basic fibroblast growth factor

CAM assay:

chorioallantoic membrane assay

cDNA:

complementary DNA

CHS:

cutaneous contact hypersensitivity

CN:

collagen

CRAd:

conditionally replicative oncolytic adenovirus

EC:

extracellular

ECM:

extracellular matrix

EGF-like:

epidermal growth factor-like

EMT:

epithelial-mesenchymal transition

F:

fibroblasts

FAK:

focal adhesion kinase

FN:

fibronectin

HA:

hyaluronic acid

HSP27:

heat shock protein 27

IL-6:

interleukin-6

ILK:

integrin-linked kinase

ip:

intraperitoneal

iv:

intravenous

L:

leukocytes

LN:

laminin

LPA:

lysophosphatidic acid

LPS:

lipopolysaccharide

M:

methylated

MCP-1:

monocyte chemoattractant protein

ME:

methylation

mets:

metastases

MLL gene:

mixed lineage leukemia gene

MMP(s):

matrix metalloproteinase(s)

Mo:

macrophages

mRNA:

messenger RNA

MT1-MMP:

membrane type 1- matrix metalloproteinase

MVD:

microvascular density

N:

neutrophils

NC:

no change

NF-kappaB:

nuclear factor kappaB

P:

pericytes

p38 MAPK:

p38 mitogen activated protein kinase

PDGF:

platelet-derived growth factor

PGE2:

prostaglandin E2

PMN(s):

polymorphonuclear leukocyte(s)

[R]:

VEGF receptor

sc:

subcutaneous

shRNA:

short hairpin RNA

siRNA:

short interfering RNA

SPARC:

secreted protein acidic and rich in cysteine

TGF-beta:

transforming growth factor-beta

THR:

T/tAg, hTERT, H-rasV12G

TIMP:

tissue inhibitor of metalloproteinase

TRAMP:

transgenic adenocarcinoma of mouse prostate

U:

unmethylated

uPA:

urokinase plasminogen activator

uPAR:

uPA receptor

VN:

vitronectin

VEGF:

vascular endothelial growth factor

wt:

wild-type

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Authors and Affiliations

  1. Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, 48202, Detroit, MI, USA

    Stacey L. Thomas & Sandra A. Rempel

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  1. Stacey L. Thomas
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  2. Sandra A. Rempel
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Correspondence to Sandra A. Rempel .

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

    Margareta M. Mueller

  2. Am Pferchelhang 32, Heidelberg, 69118, Germany

    Norbert E. Fusenig

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Thomas, S.L., Rempel, S.A. (2011). SPARC and the Tumor Microenvironment. 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_17

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