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.
Abstract
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.
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https://hdl.handle.net/10161/4370Published Version (Please cite this version)
10.1186/1478-811X-8-10Publication Info
Moore, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Stanley J. Robboy
Professor Emeritus of Pathology
My research program, largely histopathological, concerns definitions of criteria,
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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
David Keith Walmer
Adjunct Professor 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
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strategies that can be Developing a center of excellence for women's health in rural
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