Thyroid Epithelial Morphogenesis in Vitro: A Role for Bumetanide-Sensitive Cl- Secretion during Follicular Lumen Development

Yap, Alpha; Stevenson, Bruce R.; Armstrong, Jason W.; Keast, Janet R.; Manley, S. W.

doi:10.1006/excr.1994.1205

Cited by 20 publications

(10 citation statements)

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“…Furthermore, in vitro models for differentiation show that the cotransport activity is either attenuated following terminal differentiation (Delpire and Gullans, 1994;Leung et al, 1994), or that its inhibition by bumetanide inhibits differentiation (Yap et al, 1994).…”

Section: Introductionmentioning

confidence: 97%

Localization of a Na+-K+-2Cl− Cotransporter in the Rabbit Lens

Alvarez¹,

Candia

Turner³

et al. 2001

Experimental Eye Research

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Section: Introductionmentioning

confidence: 97%

Localization of a Na+-K+-2Cl− Cotransporter in the Rabbit Lens

Alvarez¹,

Candia

Turner³

et al. 2001

Experimental Eye Research

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“…Lumen can also be created without apoptosis. For example, separation of opposing membranes results in the generation of small lumens during thyroid cyst development in 3D culture [Yap et al, 1994], which may explain the formation of small lumens in some primary hepatocyte aggregations. We showed here that the large lumen structure is the bile canaliculus with bile excretion experiment, even though hepatocytes usually form small bile canaliculi in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike 2D cultures, the 3D culture provides a unique opportunity to model the architecture of epithelium in vitro. Mammary epithelial cells in 3D culture form growth-arrested polarized acini with a hollow lumen [Debnath et al, 2002], human salivary gland cells are capable of morphogenesis and differentiation to cysts in 3D culture [Joraku et al, 2007;Szlavik et al, 2008], thyroid cells organize into follicles [Toda and Sugihara, 1990;Yap et al, 1994], and Madin-Darby Canine Kidney (MDCK) cells form cysts and tubules [Pollack et al, 1998;Lin et al, 1999] in 3D cultures. Apoptosis has been shown to be critical for creating luminal space during acinar morphogenesis in MCF-10A mammary gland [Debnath et al, 2002] and HSG salivary gland 3D cultures [Szlavik et al, 2008].…”

mentioning

confidence: 99%

QSG‐7701 human hepatocytes form polarized acini in three‐dimensional culture

Zhang

Zhao

2010

J of Cellular Biochemistry

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Hepatocytes are polarized and fulfill a variety of liver-specific functions in vivo; but the polarized tissue structure and many of these functions are lost when the cells are cultured on plastic. To recapitulate the polarized structure and tissue-specific function of liver cells in culture, we established a three-dimensional (3D) culture assay with the human hepatocyte line QSG-7701. In 3D Matrigel culture, QSG-7701 cells formed polarized spheroids with a center lumen, which is reminiscent of bile canaliculi in the liver. Immunofluoresence analysis showed that F-actin bundles and radixin were mainly located at the apical membrane and that alpha6 and beta1 integrins were localized basally in 3D culture. Lumen formation was associated with the selective apoptosis of centrally located cells and was accompanied by proliferative suppression during acinar development. Compared to QSG-7701 cells in 2D or agarose gel cultures, the cells in 3D Matrigel culture maintained a given direction of biliary excretion and acquired higher levels of cytochrome P450 and albumin expression. Our study shows that the immortal human hepatocytes, QSG-7701, in 3D Matrigel culture reacquire cardinal features of glandular epithelium in vivo, providing an ex vivo model to study liver-specific function and tumorigenesis.

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“…To facilitate their analysis, it is useful to divide the process of lumenogenesis into two phases: initial lumen formation and subsequent lumen expansion (for details, see Yap et al, 1994). Initial lumen formation is thought to be the direct consequence of cell polarization.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, it has been proposed that when epithelial cells within a 3D aggregate begin to polarize, intracellular vacuoles containing apical membrane proteins fuse with the prospective apical pole, thereby forming a nascent lumen (Wang et al, 1994;Yap et al, 1995). The subsequent enlargement of the primitive cavitary structure may be due to proteolysis of the surrounding pericellular matrix Kadono et al, 1998;Obermüller et al, 2001) or to fluid accumulation resulting from vectorial transport of water and solutes by the epithelial cells lining the cavity (Grantham et al, 1989;Macias et al, 1992;Yap et al, 1994). To begin to address the mechanisms responsible for RAinduced lumen formation, we have examined in this study the potential role of matrix-remodeling proteases.…”

Section: Discussionmentioning

confidence: 99%

Retinoids induce lumen morphogenesis in mammary epithelial cells

Montesano

Soulié

2002

Journal of Cell Science

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Lumen formation is a fundamental step in the development of the structural and functional units of glandular organs, such as alveoli and ducts. In an attempt to elucidate the molecular signals that govern this morphogenetic event, we set up an in vitro system in which cloned mammary epithelial cells grown in collagen gels under serum-free conditions form solid, lumen-less colonies. Addition of as little as 0.1% donor calf serum (DCS) was sufficient to induce the formation of a central cavity. Among a number of serum constituents analyzed, retinol was found to mimic the effect of DCS in inducing lumen morphogenesis. Since the biological activities of retinol are largely dependent on its conversion to all-trans-retinoic acid (RA), we examined in more detail the effect of RA on lumen formation. RA induced the formation of lumen-containing colonies (cysts) in a concentration- and time-dependent manner, a half-maximal effect after 9 days of culture being observed with 100 pM RA. The pleiotropic effects of retinoids are mediated by nuclear retinoic acid receptors (RARs; α, β and γ) and retinoid X receptors (RXRs; α, β and γ). To identify the signaling pathway involved in RA-induced lumen formation, we used receptor-specific synthetic retinoids. TTNPB, a selective RAR agonist,promoted lumen morphogenesis, whereas RXR-selective ligands lacked this activity. Lumen formation was also induced at picomolar concentrations by Am-580, a synthetic retinoid that selectively binds the RARα receptor subtype. Moreover, co-addition of Ro 41-5253, an antagonist of RARα,abrogated the lumen-inducing activity of both RA and DCS, indicating that this biological response is mediated through an RARα-dependent signaling pathway. To gain insight into the mechanisms underlying RA-induced lumen formation, we assessed the potential role of matrix metalloproteinases (MMP). Using gelatin zymography, we observed a dose-dependent increase in latent and active forms of gelatinase B (MMP-9) upon RA treatment. In addition, lumen formation was abrogated by addition of the synthetic MMP inhibitor BB94,indicating that this morphogenetic process is likely to require MMP activity. Collectively, our results provide evidence that RA promotes lumen formation by mammary epithelial cells in vitro and suggest that it plays a similar role during mammary gland development in vivo.

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Thyroid Epithelial Morphogenesis in Vitro: A Role for Bumetanide-Sensitive Cl- Secretion during Follicular Lumen Development

Cited by 20 publications

References 0 publications

Localization of a Na+-K+-2Cl− Cotransporter in the Rabbit Lens

Localization of a Na+-K+-2Cl− Cotransporter in the Rabbit Lens

QSG‐7701 human hepatocytes form polarized acini in three‐dimensional culture

Retinoids induce lumen morphogenesis in mammary epithelial cells

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