Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Malik, Minnie; Catherino, William H.

doi:10.1016/j.fertnstert.2012.02.037

Cited by 37 publications

(37 citation statements)

References 34 publications

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“…Immunocytochemistry-Immunocytochemistry was performed using a modification of a method described previously (29). In brief, cells were seeded on poly-L-lysine-coated coverslips.…”

Section: Methodsmentioning

confidence: 99%

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

Borahay

Kılıç

Yallampalli

et al. 2014

Journal of Biological Chemistry

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Background: Statins have broad-reaching effects beyond lowering plasma lipids, including antitumor properties. Results: Simvastatin inhibits proliferation and induces calcium-dependent apoptosis of human uterine leiomyoma cells. Conclusion:We report a novel calcium-mediated pathway associated with antitumor properties of simvastatin. Significance: Simvastatin may have antitumor properties significant for the treatment of human uterine leiomyomas.

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“…Immunocytochemistry-Immunocytochemistry was performed using a modification of a method described previously (29). In brief, cells were seeded on poly-L-lysine-coated coverslips.…”

Section: Methodsmentioning

confidence: 99%

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

Borahay

Kılıç

Yallampalli

et al. 2014

Journal of Biological Chemistry

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“…34 The 18S ribosomal RNA gene was used as an internal control, and each sample was analyzed in triplicate. Bio-Rad iCycler software, version 3.1, was used for data analysis.…”

Section: Quantitative Reverse Transcriptase Polymerase Chain Reactionmentioning

confidence: 99%

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

et al. 2014

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Uterine leiomyomata are common benign tumors in women of reproductive age and demonstrate an attenuated response to mechanical signaling that involves Rho and integrins. To further characterize the impairment in Rho signaling, we studied the effect of Rho-kinase inhibitor, fasudil, on extracellular matrix production, in 2-dimensional (2D) and 3-dimensional (3D) cultures of leiomyoma and myometrial cells. Leiomyoma 2D cultures demonstrated a rapid decrease in gene transcripts and protein for fibronectin, procollagen 1A, and versican. In 3D cultures, fibronectin and procollagen 1A proteins demonstrated increased levels at lower concentrations of fasudil, followed by a concentration-dependent decrease. Versican protein increased up to 3-fold, whereas fibromodulin demonstrated a significant decrease of 1.92-fold. Myometrial 2D or 3D cultures demonstrated a decrease in all proteins after 72 hours of treatment. The 3D leiomyoma cultures demonstrated a significant increase in active RhoA, followed by a concentration-dependent decrease at higher concentrations. A concentration-dependent increase in phosphoextracellular regulated signal kinase and proapoptotic protein Bax was observed in 3D leiomyoma cultures. Fasudil relaxed the contraction of the 3D collagen gels caused by myometrium and leiomyoma cell growth. These findings indicate that the altered state of Rho signaling in leiomyoma was more clearly observed in 3D cultures. The results also suggest that fasudil may have clinical applicability for treatment of uterine leiomyoma.

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“…Growth factor genes (EGF, HB-EGF, VEGF, bFGF,PDGF, TGF-b, and ADM) are differentially expressed in LM compared with normal myometrium [Tal and Segars 2014]. VEGF, EGF, heparin binding epidermal growth factor (HB-EGF), PDGF, IGF, TGF-α, TGF-β, acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF), and their receptors have been demonstrated to play a crucial role in UL growth [Norian et al 2009;Malik and Catherino 2012]. Some growth factors are known as inducers of mitogenesis and differentiation of mesodermal cells, including fibroblasts, stem myoblast cells (SMCs), and endothelial cells.…”

Section: Gene Interactions: Ulmentioning

confidence: 99%

Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin?

Baranov

Ivaschenko

Yarmolinskaya

2016

Systems Biology in Reproductive Medicine

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Endometriosis (EM) and uterine leiomyoma (UL) are two most frequent benign tumors of monoclonal origin affecting about 30% of all women in their reproductive age. Modern molecular technologies have made a tremendous impact in understanding both disorders. Here is the first comparative analysis of molecular mechanisms underlying development of EM and UL as it looks from the platform of systems genetics. Similarities and differences of EM and UL at their incipient stages are enlightened with special emphasis on their gene networks, gene expression, and epigenetic regulation, of pathologic development. The analysis substantiates a new hypothesis postulating tumors as outgrowths of the stem cells with mesenchymal commitment lineage (mSC) which migrate from the endometrium/myometrium junctional zone of the uterus. Comparative analysis has revealed basic similarities of molecular pathogenesis of EM and UL suggesting molecular syntropy of both disorders. Peculiarities of the epigenetic landscape determining development of mSC may explain the existence of different clinical forms of EM and UL as well as their unique clinical manifestation. Some perspectives for practical and scientific application in EM and UL studies of this new hypothesis are outlined.

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Development and validation of a three-dimensional in vitro model for uterine leiomyoma and patient-matched myometrium

Cited by 37 publications

References 34 publications

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells

Leiomyoma Cells in 3-Dimensional Cultures Demonstrate an Attenuated Response to Fasudil, a Rho-Kinase Inhibitor, When Compared to 2-Dimensional Cultures

Comparative systems genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin?

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