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Matrix production and remodeling as therapeutic targets for uterine leiomyoma

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Uterine leiomyoma, commonly known as fibroids, is a benign neoplasm of smooth muscle in women. The incidence of clinically symptomatic fibroids in reproductive-age women is approximately 20 %, with nearly 80 % of black women suffering from this condition. Symptoms include severe pain and hemorrhage; fibroids are also a major cause of infertility or sub-fertility in women. Uterine leiomyoma consist of hyperplastic smooth muscle cells and an excess deposition of extracellular matrix, specifically collagen, fibronectin, and sulfated proteoglycans. Extracellular matrix components interact and signal through integrin-β1 on the surface of uterine leiomyoma smooth muscle cells, provide growth factor storage, and act as co-receptors for growth factor-receptor binding. ECM and growth factor signaling through integrin-β1 and growth factor receptors significantly increases cell proliferation and ECM deposition in uterine leiomyoma. Growth factors TGF-β, IGF, PDGF, FGF and EGF are all shown to promote uterine leiomyoma progression and signal through multiple pathways to increase the expression of genes encoding matrix or matrix-modifying proteins. Decreasing integrin expression, reducing growth factor action and inhibiting ECM action on uterine leiomyoma smooth muscle cells are important opportunities to treat uterine leiomyoma without use of the current surgical procedures. Both natural compounds and chemicals are shown to decrease fibrosis and uterine leiomyoma progression, but further analysis is needed to make inroads in treating this common women’s health issue.

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Abbreviations

AKAP:

A-kinase anchor protein

Bcl:

Burkitt cell lymphoma

CDK:

cell division kinase

ECM:

extracellular matrix

EGF:

epidermal growth factor

Erk:

extacellular signal-regulated kinase

FGF:

fibroblast growth factor

FGFR:

fibroblast growth factor receptor

HSPG:

heparan sulfate proteoglycan

IGF:

insulin-like growth factor

IGFBP:

insulin-like growth factor binding protein

MAPK:

mitosis-activating protein kinase

MMP:

matrix metalloprotease

PDGF:

platelet-derived growth factor

SB:

Scutellaria barbata D. Don

SMC:

smooth muscle cells

TGF:

transforming growth factor

UAE:

uterine artery embolization

UL:

uterine leiomyoma

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Acknowledgements

The authors wish to acknowledge Russell Fujisawa for his generous assistance in editing this manuscript. We also thank Dr. Margery Beinfeld for reading the manuscript and providing helpful suggestions.

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  1. Public Heath and Professional Degrees Program, Tufts University School of Medicine, Boston, MA, 02111, USA

    Caitlin Fujisawa

  2. Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA

    John J. Castellot Jr

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  1. Caitlin Fujisawa
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Correspondence to John J. Castellot Jr.

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Fujisawa, C., Castellot, J.J. Matrix production and remodeling as therapeutic targets for uterine leiomyoma. J. Cell Commun. Signal. 8, 179–194 (2014). https://doi.org/10.1007/s12079-014-0234-x

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