TITLE

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

AUTHOR(S)
Moore, Alicia B.; Linda Yu; Swartz, Carol D.; Xaiolin Zheng; Lu Wang; Castro, Lysandra; Kissling, Grace E.; Walmer, David K.; Robboy, Stanley J.; Dixon, Darlene
PUB. DATE
January 2010
SOURCE
Cell Communication & Signaling;2010, Vol. 8, p10
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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, phosphomitogen 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.
ACCESSION #
52858288

 

Related Articles

  • Catechol-O-Methyltransferase Expression and 2-Methoxyestradiol Affect Microtubule Dynamics and Modify Steroid Receptor Signaling in Leiomyoma Cells. Salama, Salama A.; Kamel, Marwa W.; Botting, Shaleen; Salih, Sana M.; Borahay, Mostafa A.; Hamed, Ahmed A.; Kilic, Gokhan S.; Saeed, Muhammad; Williams, Marian Y.; Diaz-Arrastia, Concepcion R. // PLoS ONE;2009, Vol. 4 Issue 10, p1 

    Context: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2- Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-Omethyltransferase (COMT). Our previous study demonstrated that 2ME is...

  • F-FDG PET/CT findings in uterine leiomyomas. Jehanno, N.; Wartski, M.; Malhaire, C.; Fréneaux, P.; Petras, S.; Alberini, J. // European Journal of Nuclear Medicine & Molecular Imaging;May2014, Vol. 41 Issue 5, p1034 

    Several photographs are presented depicting the positron emission tomography (PE) or computer tomography (CT) images of the 43-year-old woman who was diagnosed with uterine leiomyomas.

  • EMBOLIZACIÓN DE ARTERIAS UTERINAS EN EL TRATAMIENTO DE MIOMAS UTERINOS SINTOMÁTICOS. Z., Soledad Loyola; P., Mario Fava; P., Rodrigo Macaya; Q., Luis Meneses // Revista Chilena de Obstetricia y Ginecología;2007, Vol. 72 Issue 4, p236 

    Uterine fibroids may cause menorrhagia, infertility and a pressure effect over other pelvic organs. Uterine artery embolization (UAE) is a minimally invasive technique for treating fibroids. It has become a therapeutic alternative to hysterectomy and multiple myomectomy, for the treatment of...

  • Successful pregnancies with uterine leiomyomas and myomectomy at the time of caesarean section. Yu-Lan Mu // Postgraduate Medical Journal;Sep2011, Vol. 87 Issue 1031, p601 

    OBJECTIVE: To ascertain the impact of uterine leiomyomas on pregnancy outcome, and to determine the effectiveness of myomectomy at the time of caesarean delivery. METHODS: A retrospective study was conducted on pregnant women with uterine leiomyomas. Clinical information including the course of...

  • Expression of Ki-67, P53 and Progesterone Receptors in Uterine Smooth Muscle Tumors. Diagnostic Value. Petrović, Davor; Babić, Damir; Forko, Jadranka Ilić; Martinac, Ivana // Collegium Antropologicum;Mar2010, Vol. 34 Issue 1, p93 

    Aim was to investigate expression of Ki-67, P53 and progesterone receptors (PR) in leiomyomas (LM), smooth muscle tumors of uncertain malignant potential (STUMP) and leiomyosarcomas (LMS) and to establish possible usefulness of these three parameters in distinguishing between LM and STUMP, and...

  • Pathogenesis of Endometriosis and Uterine Fibroids. Ciarmela, Pasquapina; Critchley, Hilary; Christman, Gregory M.; Reis, Fernando M. // Obstetrics & Gynecology International;2013, p1 

    No abstract available.

  • INVESTIGATIONS ON UTERINE FATTY LESIONS. SOŚNIK, HENRYK; SOŚNIK, KATARZYNA // Polish Journal of Pathology: Official Journal of the Polish Soci;2013, Issue 2, p136 

    Uterine fatty lesions (UFLs) continue to arouse great interest because of their rare occurrence and unknown histogenesis. The aim of the study was to determine the occurrence of UFLs and the dynamics of their development, as well as to evaluate the histopathology and relationship with regressive...

  • Fibroid embolization and high-intensity focused U/S. Betjes, Heleen E.; Stewart, Elizabeth A. // Contemporary OB/GYN;Apr2007 Special Issue, Vol. 52, p14 

    The article investigates the efficacy of magnetic resonance imaging-guided focused ultrasound surgery and uterine artery embolization, two of the latest therapies for women with uterine fibroids. Information on the Uterine Fibroid Symptom Quality of Life Instrument is provided. An overview of...

  • Higher Rate of Partial Devascularization and Clinical Failure After Uterine Artery Embolization for Fibroids with Spherical Polyvinyl Alcohol. Golzarian, Jafar; Lang, Elvira; Hovsepian, David; Kroncke, Thomas; Lampmann, Leo; Lohle, Paul; Pelage, Jean-Pierre; Shlansky-Goldberg, Richard; Valenti, David; Vorwerk, Dierk; Spies, James // CardioVascular & Interventional Radiology;Jan/Feb2006, Vol. 29 Issue 1, p1 

    The article focuses on the use of uterine fibroid embolization as a safe alternative for surgical treatment of fibroid tumors. The first embolic materials used for this minimally invasive technique were non-spherical polyvinyl alcohol particles. The author of this article encourages the use of...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics