Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture.
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BACKGROUND: Uterine leiomyomas (fibroids) are benign smooth muscle tumors that often contain an excessive extracellular matrix (ECM). In the present study, we investigated the interactions between human uterine leiomyoma (UtLM) cells and uterine leiomyoma-derived fibroblasts (FB), and their importance in cell growth and ECM protein production using a coculture system. RESULTS: We found enhanced cell proliferation, and elevated levels of ECM collagen type I and insulin-like growth factor-binding protein-3 after coculturing. There was also increased secretion of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor-2, and platelet derived growth factor A and B in the media of UtLM cells cocultured with FB. Protein arrays revealed increased phosphorylated receptor tyrosine kinases (RTKs) of the above growth factor ligands, and immunoblots showed elevated levels of the RTK downstream effector, phospho-mitogen activated protein kinase 44/42 in cocultured UtLM cells. There was also increased secretion of transforming growth factor-beta 1 and 3, and immunoprecipitated transforming growth factor-beta receptor I from cocultured UtLM cells showed elevated phosphoserine expression. The downstream effectors phospho-small mothers against decapentaplegic -2 and -3 protein (SMAD) levels were also increased in cocultured UtLM cells. However, none of the above effects were seen in normal myometrial cells cocultured with FB. The soluble factors released by tumor-derived fibroblasts and/or UtLM cells, and activation of the growth factor receptors and their pathways stimulated the proliferation of UtLM cells and enhanced the production of ECM proteins. CONCLUSIONS: These data support the importance of interactions between fibroid tumor cells and ECM fibroblasts in vivo, and the role of growth factors, and ECM proteins in the pathogenesis of uterine fibroids.
Published Version (Please cite this version)10.1186/1478-811X-8-10
Publication InfoMoore, AB; Yu, L; Swartz, CD; Zheng, X; Wang, L; Castro, L; ... Dixon, D (2010). Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture. Cell Commun Signal, 8. pp. 10. 10.1186/1478-811X-8-10. Retrieved from https://hdl.handle.net/10161/4370.
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Professor of Pathology
My research program, largely histopathological, concerns definitions of criteria, biological properties, differential diagnosis, and survival associated with pathological lesions in the female genital tract. With the gynecologic oncologists at Duke, we have reviewed the Institution's long term experience of endometrial cancer and with the International Collaborative Group on Endometrium, we have developed a new classification system for endometrial hyperplasia that better differentiates pr
Associate Professor of the Practice of Global Health
My areas of interest include both 1. women's health in Haiti & 2. reproductive endocrinology GLOBAL HEALTH Preventing cervical cancer in Haiti Goal: Develop culturally acceptable and cost effective strategies to prevent cervical cancer Description: 1) Evaluating strategies that can be Developing a center of excellence for women's health in rural HaitiDescriptionRE
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