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Myoepithelial Cells: Autocrine and Paracrine Suppressors of Breast Cancer Progression

  • Sanford H. BarskyEmail author
  • Nina J. Karlin
Article

Abstract

Host cellular paracrine regulation of tumor progression is an important determinant of tumor biology but one cell that has been ignored in this regulation is the myoepithelial cell. Myoepithelial cells surround normal ducts and precancerous lesions, especially of the breast and form a natural border separating proliferating epithelial cells from proliferating endothelial cells (angiogenesis). Myoepithelial cells may thus negatively regulate tumor invasion and metastasis. Whereas epithelial cells are susceptible targets for transforming events, myoepithelial cells are resistant. Therefore, it can be said that myoepithelial cells function as both autocrine as well as paracrine tumor suppressors. Our laboratory has found that myoepithelial cells secrete a number of suppressor molecules including high amounts of diverse proteinase inhibitors and angiogenic inhibitors but low amounts of proteinases and angiogenic factors compared to common malignant cell lines. This observation has been made in vitro, in mice, and in humans and suggests that myoepithelial cells exert pleiotropic suppressive effects on tumor progression. The gene expression profile of myoepithelial cells may explain the pronounced anti-invasive and anti-angiogenic effects of myoepithelial cells on carcinoma cells and may also account for the reduced malignancy of myoepithelial tumors, which are devoid of appreciable angiogenesis and invasive behavior.

Key Words

myoepithelial cells tumor suppression expression profile angiogenic inhibitors proteinase inhibitors 

Abbreviations used

aFGF

acidic fibroblast growth factor

α1-AT

alpha 1-antitrypsin

5-azaC

5-azacytidine

bFGF

basic fibroblast growth factor

CALLA

common acute lymphocytic leukemia antigen

CAT

chloramphenicol acetyl transferase

CGH

comparative genomic hybridization

COL1A1

type I collagen α1 chain

COL4A1

type IV collagen α1 chain

COL4A2

type IV collagen α2 chain

CM

conditioned medium

dB-cAMP

N6,2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate

DCIS

ductal carcinoma in situ

DF

ductal lavage fluid

DMSO

dimethylsulfoxide

EHS

Engelbreth-Holm-Swarm

ER-α

estrogen receptor-α

ER-β

estrogen receptor-β

FCS

fetal calf serum

FN1

fibronectin

HB-ECGF

heparin-binding endothelial cell growth factor

HGF

hepatocyte growth factor

HIF-1α

hypoxia-inducible factor-alpha

HMEC

human mammary epithelial cells

HRE

hypoxia response element

HRT

hormone replacement therapy

HSPG2

perlecan

iNOS

inducible nitric oxide synthase

K-SFM

keratinocyte serum-free medium

LOH

loss of heterozygosity

MMP-9

matrix metalloproteinase-9

MUC-1

mucin-1

Na-But

sodium butyrate

PAI-1

plasminogen activator inhibitor-1

PD-ECGF

platelet-derived endothelial cell growth factor

PlGF

placental growth factor

PMA

phorbol 12-myristate 13-acetate: PN-II, protease nexin-II

RA

all trans retinoic acid

TIMP-1

tissue inhibitor of metalloproteinase-1

TFGα

transforming growth factor α

TGFβ

transforming growth factor β

TNFα

tumor necrosis factor α

UVE

human umbilical vein endothelial cells

uPA

urokinase-type plasminogen activator

VEGF

vascular endothelial growth factor

vWf

von Willebrand factor

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of PathologyThe Ohio State University College of MedicineColumbus
  2. 2.Department of Medicine, Division of Hematology-OncologyUCLA-Olive View Medical CenterSylmar
  3. 3.Department of PathologyThe Ohio State University College of MedicineColumbus

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