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The incidence of clinically symptomatic fibroids in reproductive\u2010age 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\u2010fertility 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\u2010\u03b21 on the surface of uterine leiomyoma smooth muscle cells, provide growth factor storage, and act as co\u2010receptors for growth factor\u2010receptor binding. ECM and growth factor signaling through integrin\u2010\u03b21 and growth factor receptors significantly increases cell proliferation and ECM deposition in uterine leiomyoma. Growth factors TGF\u2010\u03b2, 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\u2010modifying 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. 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