Dynamic analysis of hepatoma spheroid formation: roles of E-cadherin and β1-integrin

Lin, Ruei-Zeng; Chou, Li‐Fang; Chien, Chichen Michael; Chang, Hwan‐You

doi:10.1007/s00441-005-0148-2

Cited by 272 publications

(230 citation statements)

References 44 publications

(54 reference statements)

Supporting

Mentioning

201

Contrasting

Unclassified

Order By: Relevance

“…In contrast, downregulation of E-cadherin function causes reduced viability, suggesting that proliferation signals downstream of E-cadherin activation contribute to ovarian cancer cell survival. Similar results have been observed in squamous cell carcinoma [89], hepatoma [90] and Ewing tumor cells [91].…”

Section: Functional Impact Of Phenotypic Plasticity: Why Gain E-cadhesupporting

confidence: 88%

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Hudson

Zeineldin

Stack

2008

Clin Exp Metastasis

165

172

View full text Add to dashboard Cite

The mesodermally derived normal ovarian surface epithelium (OSE) displays both epithelial and mesenchymal characteristics and exhibits remarkable phenotypic plasticity during post-ovulatory repair. The majority of epithelial ovarian carcinomas (EOC) are derived from the OSE and represent the most lethal of all gynecological malignancies, as most patients (~70%) present at diagnosis with disseminated intra-abdominal metastasis. The predominant pattern of EOC metastasis involves pelvic dissemination rather than lymphatic or hematologic spread, distinguishing EOC from other solid tumors. Acquisition of the metastatic phenotype involves a complex series of interrelated cellular events leading to dissociation (shedding) and dispersal of malignant cells. A key event in this process is disruption of cell-cell contacts via modulation of intercellular junctional components. In contrast to most carcinomas that downregulate E-cadherin expression during tumor progression, an unique feature of primary well-differentiated ovarian cancers is a gain of epithelial features, characterized by an increase in expression of E-cadherin. Subsequent reacquisition of mesenchymal features is observed in more advanced tumors with concomitant loss of E-cadherin expression and/ or function during progression to metastasis. The functional consequences of this remarkable phenotypic plasticity are not fully understood, but may play a role in modulation of cell survival in suspension (ascites), chemoresistance, and intraperitoneal anchoring of metastatic lesions. Keywords ovarian cancer; epithelium; cadherin; keratin; vimentin; epithelial-mesenchymal transition; plasticity Ovarian Cancer-OverviewTumors arising from the ovarian epithelium account for ~90% of ovarian malignancies and epithelial ovarian carcinoma (EOC) is the leading cause of death from gynecologic malignancy, resulting in approximately 15,280 deaths in the United States alone in 2006 [1]. These distressing statistics are largely due to the low detection rate of disease confined to the ovary (stage 1) when 5-year survival is >90%. Approximately 75% of women are initially diagnosed with disseminated intra-abdominal disease (stage III-IV) and have a 5-year survival of <20%.Ovarian tumors are pathologically heterogeneous with four major histotypes: serous, endometroid, clear cell and mucinous. These classifications are histogenetically based on The early steps of EOC metastasis involve shedding of the cells from the primary tumor to form free floating cells or multi-cellular aggregates (MCAs) in ascites [ Fig. 1]. Cell-cell and cell-matrix adhesion molecules mediate interaction of metastasizing tumor cells with mesothelial cells lining the inner surface of the peritoneal cavity and the sub-mesothelial extracellular matrix (ECM). Localized proteolytic degradation of sub-mesothelial ECM components facilitates migration of tumor cells and anchoring of secondary lesions on adjacent pelvic organs, and at later stages, metastasis to distant organs [9,10]. However, the majority of wo...

show abstract

Section: Functional Impact Of Phenotypic Plasticity: Why Gain E-cadhesupporting

confidence: 88%

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Hudson

Zeineldin

Stack

2008

Clin Exp Metastasis

165

172

View full text Add to dashboard Cite

show abstract

“…This was in contrast with the activation of EMT pathway [45] but in consistent with the expression of liver cancer tissue used in this study. Previously study also shows E-cadherin regulates the establishment of the adherens junctions and the expression of E-cadherin is upregulated when forming compact tumor spheroids [46]. The upregulation of E-cadherin expression in HCC cells cultured within ALG beads might be caused by compact spheroids formation (Fig.…”

Section: Discussionmentioning

confidence: 72%

Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

Liu

et al. 2013

Experimental Cell Research

View full text Add to dashboard Cite

“…Long-term live cell imaging showed that the expression of N-cadherin led to an increase in the rate of cell aggregation compared with untransfected involves integrin -ECM interactions and only in the later stages-after 20 h-are cadherin interactions considered to contribute to the process [23]. However, these results could be cell-type specific.…”

Section: Intercellular Binding-dependent Spheroid Formationmentioning

confidence: 99%

Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions

Garg

Fischer

Schuman

et al. 2015

J. R. Soc. Interface.

View full text Add to dashboard Cite

Cadherin interactions ensure the correct registry and anchorage of cells during tissue formation. Along the plasma membrane, cadherins form inter-junctional lattices via cis-and trans-dimerization. While structural studies have provided models for cadherin interactions, the molecular nature of cadherin binding in vivo remains unexplored. We undertook a multi-disciplinary approach combining live cell imaging of three-dimensional cell assemblies (spheroids) with a computational model to study the dynamics of N-cadherin interactions. Using a loss-of-function strategy, we demonstrate that each N-cadherin interface plays a distinct role in spheroid formation. We found that cis-dimerization is not a prerequisite for trans-interactions, but rather modulates trans-interfaces to ensure tissue stability. Using a model of N-cadherin junction dynamics, we show that the absence of cis-interactions results in low junction stability and loss of tissue integrity. By quantifying the binding and unbinding dynamics of the N-cadherin binding interfaces, we determined that mutating either interface results in a 10-fold increase in the dissociation constant. These findings provide new quantitative information on the steps driving cadherin intercellular adhesion and demonstrate the role of cis-interactions in junction stability.

show abstract

Dynamic analysis of hepatoma spheroid formation: roles of E-cadherin and β1-integrin

Cited by 272 publications

References 44 publications

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens junctions

Contact Info

Product

Resources

About