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Extracellular Matrix Composition Reveals Complex and Dynamic Stromal-Epithelial Interactions in the Mammary Gland

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Abstract

The mammary gland is an excellent model system to study the interplay between stroma and epithelial cells because of the gland’s unique postnatal development and its distinct functional states. This review focuses on the contribution of the extracellular matrix (ECM) to stromal-epithelial interactions in the mammary gland. We describe how ECM physical properties, protein composition, and proteolytic state impact mammary gland architecture as well as provide instructive cues that influence the function of mammary epithelial cells during pubertal gland development and throughout adulthood. Further, based on recent proteomic analyses of mammary ECM, we describe known mammary ECM proteins and their potential functions, as well as describe several ECM proteins not previously recognized in this organ. ECM proteins are discussed in the context of the morphologically-distinct stromal subcompartments: the basal lamina, the intra- and interlobular stroma, and the fibrous connective tissue. Future studies aimed at in-depth qualitative and quantitative characterization of mammary ECM within these various subcompartments is required to better elucidate the function of ECM in normal as well as in pathological breast tissue.

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Abbreviations

collagen IV:

type IV collagen

DDR1:

discoidin domain receptor 1

EM:

electron microscopy

EGFR:

epidermal growth factor receptor

ECM:

extracellular matrix

ED:

extra domain

FACIT:

fibril associated collagens with interrupted triple helices

FGF:

fibroblast growth factor

FN:

fibronectin

GAG:

glycosaminoglycan

H&E:

hematoxylin and eosin stain

HGF:

hepatocyte growth factor

LN:

laminin

LAP:

latency-associated peptide

LRR:

leucine-rich repeats

LOX:

lysyl oxidase

MMP:

matrix metalloproteinase

MAGP:

microfibril-associated glycoprotein

MCP-1:

monocyte chemoattractant protein-1

SPARC:

secreted protein acidic and rich in cysteine

SLRP:

small leucine-rich proteoglycan

SD:

Sprague Dawley

TN:

tenascin

tTG2:

tissue transglutaminase 2

TGF-β:

transforming growth factor β

TLR:

toll like receptor

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Acknowledgment

We thank Jenean O’Brien and Jaime Fornetti for critical review of the manuscript. We also thank Dr. Gilbert H. Smith (National Institutes of Health, MD) for providing us with the electron micrograph image in figure 1.

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  1. Department of Medicine, Division of Medical Oncology, University of Colorado Denver, MS8117, RC-1S, 8401K, 12801 E 17th Ave, Aurora, CO, 80045, USA

    Ori Maller, Holly Martinson & Pepper Schedin

  2. Program in Cancer Biology, University of Colorado Denver, MS8104, RC-1S, 5117, 12801 E 17th Ave, Aurora, CO, 80045, USA

    Ori Maller, Holly Martinson & Pepper Schedin

  3. University of Colorado Cancer Center, Bldg 500, Suite 6004C, 13001 E 17th Place, Aurora, CO, 80045, USA

    Pepper Schedin

  4. AMC Cancer Research Center, Bldg 500, Suite 6004C, 13001 E 17th Place, Aurora, CO, 80045, USA

    Pepper Schedin

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  1. Ori Maller
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Correspondence to Pepper Schedin.

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Supported by Department of Defense Idea Award#BC095850 to PS.

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Maller, O., Martinson, H. & Schedin, P. Extracellular Matrix Composition Reveals Complex and Dynamic Stromal-Epithelial Interactions in the Mammary Gland. J Mammary Gland Biol Neoplasia 15, 301–318 (2010). https://doi.org/10.1007/s10911-010-9189-6

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