We are analyzing https://link.springer.com/article/10.1186/1478-811x-8-10.

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 | Cell Communication and Signaling
Description:
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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Keywords {🔍}

cells, utlm, growth, uterine, cell, cocultured, leiomyoma, article, expression, pubmed, cultured, google, scholar, figure, utsmc, increased, fibroblasts, compared, cas, ecm, proliferation, factors, factor, media, human, tumor, significant, igfbp, receptor, tgfβ, leiomyomas, muscle, collagen, smooth, protein, proteins, levels, data, signaling, normal, pcna, increase, production, activation, coculture, fibroids, study, authors, type, phosphorylated,

Topics {✒️}

transforming growth factor-beta transforming growth factor-beta1 transforming growth factor-beta3 platelet-derived growth factor gonadotropin-releasing hormone analog van buul-offers sc protein kinase-dependent pathway article download pdf sex hormone-binding globulin uterine leiomyoma-derived fibroblasts growth factor-binding protein-3 hepatic growth factor-receptor uterine-leiomyoma-derived fb van der burg open access article inbred/outbred rodent models promising anti-fibrotic effects gonadotropin releasing hormone human breast-cancer cells stimulate cell proliferation phosphorylated receptors v-erb heparin-binding growth factors human uterine leiomyoma receptor tyrosine kinases human subjects research phosphorylated tgf-β receptor tgf-β/smad pathway fibroblast growth factor-2 human uterine tissues human uterine leiomyomas myometrial cell lines uterine leiomyoma tissues smooth muscle cells 17-beta estradiol elicits uterine leiomyoma compared epidermal growth factor leiomyoma-derived fibroblasts 7000 donkey anti-goat growth factor ligands privacy choices/manage cookies growth-promoting effects observed enhanced cell proliferation brown nuclear staining smooth muscle component cell proliferation based activated tgf-βri messenger ribonucleic acid van eijck ch van koetsveld pm authors’ original file

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         description: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. 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. 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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            Leiomyoma
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            Uterine Leiomyoma
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            Cell Biology
            Protein-Ligand Interactions
            Receptors
            Cytokines and Growth Factors
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      headline: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
      description: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. 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. 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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         Proliferate Cell Nuclear Antigen
         Leiomyoma
         Uterine Fibroid
         Uterine Leiomyoma
         Uterine Leiomyomas
         Cell Biology
         Protein-Ligand Interactions
         Receptors
         Cytokines and Growth Factors
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      name:Integrated Laboratory Systems, Incorporated, RTP, USA
      name:Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park (RTP), USA
      name:Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park (RTP), USA
      name:Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park (RTP), USA
      name:Biostatistics Branch, NIEHS, NIH, DHHS, RTP, USA
      name:Department of Obstetrics and Gynecology, Duke University Medical Center (DUMC), Duke University, Durham, USA
      name:Department of Obstetrics and Gynecology, Duke University Medical Center (DUMC), Duke University, Durham, USA
      name:Department of Pathology, DUMC, Duke University, Durham, USA
      name:Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park (RTP), USA

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