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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2010-06-10
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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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Moore, AB, L Yu, CD Swartz, X Zheng, L Wang, L Castro, GE Kissling, DK Walmer, et al. (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. p. 10. 10.1186/1478-811X-8-10 Retrieved from https://hdl.handle.net/10161/4370.
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Scholars@Duke
David Keith Walmer
My areas of interest include
women's health in Haiti
- cervical cancer prevention
- maternal child health
- hypertension
GLOBAL HEALTH
Preventing cervical cancer in Haiti
Goal: Develop culturally acceptable and cost effective strategies to prevent cervical cancer
Current strategy:
- primary screen: HPV testing
- treatment thermal ablation of the cervical transformation zone in HPV+ women
Under investigation
- strategies to remove inflammatory cells from cervical cytology
- strategies to speed up and improve AI interpretation of cervical cytology
- strategies to employ drones to deliver test kits and patient samples to deliver health care in gang controlled areas
Improving maternal child health in rural Haiti
- establishing 24/7 access to L&D services in a remote mountain community
Stanley J. Robboy
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 precancerous from benign lesions. In a nationwide NIH study in which I head the pathology review, long term complications in both sons and daughters from prenatal exposure to DES are being assessed. A major initiative is a study of vulvar dermatoses and unusual vulvar neoplasms. A final clinical pathologic correlation study, ongoing for over 40 years, has been the long term follow-up of a very rare tumor (malignant struma ovarii). Long term study has been required to identify those features that will ultimately prove to be of biologic significance for defining cases which will likely recur.
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