Hormone/growth factor interactions mediating epithelial/stromal communication in mammary gland development and carcinogenesis

Imagawa, Walter; Pedchenko, Vadim; Helber, Jennifer; Zhang, Hongzheng

doi:10.1016/s0960-0760(01)00188-1

Cited by 80 publications

(70 citation statements)

References 156 publications

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“…In this process, hUECs express various factors including cell adhesion molecules, growth factors and cytokines that have critical roles in embryo proliferation, attachment and invasion (Aplin 1997, Lessey 2000, Selam et al 2002, Nardo et al 2003. Many factors that regulate the growth of cells are also expressed from not only hUECs but also hBPCs (Imagawa et al 2002, Palmieri et al 2003 and hEFs (Ellis et al 1997, Chang et al 2002. The various factors expressed in each cell type may have an important role in inducing the growth and inhibiting the differentiation of hESCs.…”

Section: Discussionmentioning

confidence: 99%

Available human feeder cells for the maintenance of human embryonic stem cells

Lee

Song²,

Lee³

et al. 2004

Reproduction

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Mouse embryonic fibroblasts (MEFs) have been previously used as feeder cells to support the growth of human embryonic stem cells (hESCs). In this study, human adult uterine endometrial cells (hUECs), human adult breast parenchymal cells (hBPCs) and embryonic fibroblasts (hEFs) were tested as feeder cells for supporting the growth of hESCs to prevent the possibility of contamination from animal feeder cells. Cultured hUECs, hBPCs and hEFs were mitotically inactivated and then plated. hESCs (Miz-hES1, NIH registered) initially established on mouse feeder layers were transferred onto each human feeder layer and split every 5 days. The morphology, expression of specific markers and differentiation capacity of hESCs adapted on each human feeder layer were examined. On hUEC, hBPC and hEF feeder layers, hESCs proliferated for more than 90, 50 and 80 passages respectively. Human feeder-based hESCs were positive for stage-specific embryonic antigen (SSEA)-3 and -4, and Apase; they also showed similar differentiation capacity to MEF-based hESCs, as assessed by the formation of teratomas and expression of tissue-specific markers. However, hESCs cultured on hUEC and hEF feeders were slightly thinner and flatter than MEF-or hBPC-based hESCs. Our results suggest that, like MEF feeder layers, human feeder layers can support the proliferation of hESCs without differentiation. Human feeder cells have the advantage of supporting more passages than when MEFs are used as feeder cells, because hESCs can be uniformly maintained in the undifferentiated stage until they pass through senescence. hESCs established and/or maintained under stable xeno-free culture conditions will be helpful to cell-based therapy.

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Section: Discussionmentioning

confidence: 99%

Available human feeder cells for the maintenance of human embryonic stem cells

Lee

Song²,

Lee³

et al. 2004

Reproduction

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“…All of the growth factors and cytokines tested in the present work are involved in mammary gland morphogenesis (37). Although g6CM may contain several of these factors, only KGF and HGF/SF are known to be secreted exclusively by mammary stroma and to bind their receptors in epithelial cells (38). Furthermore, HGF/SF is the only one that induced changes in FN alternative splicing as well as cell scattering similar to g6CM in SCp2 cells (data not shown).…”

Section: Extracellular Regulation Of Fn Edi Alternative Splicing Is Amentioning

confidence: 92%

Mammary Epithelial-Mesenchymal Interaction Regulates Fibronectin Alternative Splicing via Phosphatidylinositol 3-Kinase

Blaustein

Pelisch

Coso

et al. 2004

Journal of Biological Chemistry

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The way alternative splicing is regulated within tissues is not understood. A relevant model of this process is provided by fibronectin, an important extracellular matrix protein that plays a key role in cell adhesion and migration and contains three alternatively spliced regions known as EDI, EDII, and IIICS. We used a cell culture system to simulate mammary epithelial-stromal communication, a process that is crucial for patterning and function of the mammary gland, and studied the effects of extracellular signals on the regulation of fibronectin pre-mRNA alternative splicing. We found that soluble factors from a mammary mesenchymal cell-conditioned medium, as well as the growth factors HGF/SF (hepatocyte growth factor/scatter factor), KGF (keratinocyte growth factor), and aFGF (acidic fibroblast growth factor), stimulate EDI and IIICS but not EDII inclusion into fibronectin mRNA in the mammary epithelial cell line SCp2, favoring fibronectin isoforms associated with proliferation, migration, and tissue remodeling. We explored the signaling pathways involved in this regulation and found that the mammary mesenchymal cell-conditioned medium and HGF/SF act through a phosphatidylinositol 3-kinase-dependent cascade to alter fibronectin alternative splicing. This splicing regulation is independent from promoter structure and de novo protein synthesis but does require two exonic elements within EDI. These results shed light on how extracellular stimuli are converted into changes in splicing patterns.Pre-mRNA alternative splicing is a widespread process that regulates gene expression and is the most important source of protein diversity in vertebrates (1). Fibronectin (FN), 1 the best characterized extracellular matrix (ECM) glycoprotein, plays a key role in cell adhesive and migratory behavior related to fundamental processes such as embryogenesis, wound healing, maintenance of tissue integrity, and malignancy. Different FN polypeptides arise through an intricate pattern of alternative splicing in three regions of the single primary transcript, (from 5Ј to 3Ј) extra domain II (EDII), extra domain I (EDI), and type III connecting segment (IIICS) (also called EDB or EIIIB, EDA or EIIIA, and V region, respectively), resulting in up to 12 variants in rodents. FN alternative splicing is modulated in a cell type-, development-, and age-specific manner and therefore constitutes a paradigm for studying the regulation of this complex process (2). EDI and EDII are cassette exons, either excluded from or included into the mature FN mRNA. The third site of alternative splicing, IIICS, is subject to total inclusion, partial inclusion, or total exclusion due to the presence of an internal 3Ј splice site within this exon.In vivo EDIϩ FN is poorly represented in the ECM of adult normal tissues. However, this variant is over-expressed in developing embryos, wound healing, liver fibrosis, ovary granulosa cell proliferation, and some tumors (2, 3). It has been proposed that EDI inclusion may mediate a conformational change in the whole m...

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“…These two distinct binding sites on tumstatin suggest unique a v h 3 integrinmediated mechanisms governing the two distinct antitumor activities (91). A third proximal site, RGD site, capable of binding to a v h 3 integrin, outside the NC1 domain sequence of tumstatin, has also been proposed recently (94). How these different a v h 3 integrin sites regulate the antiangiogenic activity of tumstatin is not understood completely.…”

Section: Matrix-derived Inhibitors Of Angiogenesismentioning

confidence: 99%