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Myoepithelial Cells: Autocrine and Paracrine Suppressors of Breast Cancer Progression

Journal of Mammary Gland Biology and Neoplasia volume 10, pages 249–260 (2005)Cite this 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.

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Abbreviations

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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Author information

Affiliations

  1. Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210

    Sanford H. Barsky

  2. Department of Medicine, Division of Hematology-Oncology, UCLA-Olive View Medical Center, Sylmar, California, 91342

    Nina J. Karlin

  3. Department of Pathology, The Ohio State University College of Medicine, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio, 43210-1218

    Sanford H. Barsky

Authors
  1. Sanford H. Barsky
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  2. Nina J. Karlin
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Correspondence to Sanford H. Barsky.

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Barsky, S.H., Karlin, N.J. Myoepithelial Cells: Autocrine and Paracrine Suppressors of Breast Cancer Progression. J Mammary Gland Biol Neoplasia 10, 249–260 (2005). https://doi.org/10.1007/s10911-005-9585-5

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  • DOI: https://doi.org/10.1007/s10911-005-9585-5

Key Words

  • myoepithelial cells
  • tumor suppression
  • expression profile
  • angiogenic inhibitors
  • proteinase inhibitors