Cell-to-cell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures

• Published in: American journal of physiology: endocrinology and metabolism 2005-03, Vol.288 (3), p.E502-E509
• Main Authors: Luther, Melanie J, Davies, Emma, Muller, Dany, Harrison, Moira, Bone, Adrian J, Persaud, Shanta J, Jones, Peter M
• Format: Article
• Language: English
• Subjects: alpha Catenin; Animals; Apoptosis - physiology; beta Catenin; beta-Galactosidase - analysis; Biomarkers - metabolism; Blotting, Western; Bromodeoxyuridine - metabolism; Cadherins - metabolism; Cell Aggregation - physiology; Cell Communication - physiology; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cytoskeletal Proteins - metabolism; DNA - biosynthesis; Fas Ligand Protein; fas Receptor - metabolism; Histocytochemistry; In Situ Nick-End Labeling; Islets of Langerhans - cytology; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Ki-67 Antigen - metabolism; Membrane Glycoproteins - metabolism; Mice; Trans-Activators - metabolism; Tumor Suppressor Proteins - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00424.2004

1 -Cell Development and Function Group, Division of Reproductive Health, Endocrinology and Development, King's College London, Guy's Campus, London Bridge, London; and 2 School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, United Kingdom Submitted 6 September 2004 ; accepted in final form 9 October 2004 Cell-to-cell interactions play an important role in the development and maintenance of the -cell phenotype. Here, we have investigated whether E-cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets form by cell aggregation rather than by proliferation from individual cells and attain the size of primary mouse islets after 7 days of maintenance in culture. E-cadherin is known to mediate homotypic cell adhesion between -cells and has also been implicated in a number of cellular processes, including proliferation, apoptosis, and differentiation. E-cadherin and its associated intracellular elements, - and -catenin, were upregulated in MIN6 pseudoislets. Pseudoislet formation was associated with an increased expression of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67, suggesting an overall reduction in cellular proliferation. However, measurements of 5-bromo-2'-deoxyuridine incorporation revealed that there were no differences in the rate of MIN6 cell proliferation whether they were configured as monolayers or as pseudoislets, which is likely to be a result of their being a transformed cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to be upregulated in the islet-like structures. However, no differential expression of Fas and FasL was detected in monolayers and pseudoislets. These results suggest that cell-to-cell interactions within islet-like structures may initiate antiproliferative and proapoptotic signals. islets of Langerhans; cell adhesion; E-cadherin; proliferation; pseudoislets Address for reprint requests and other correspondence: M. Luther, -Cell Development and Function Group, Division of Reproductive Health, Endocrinology and Development, Hodgkin Bldg., King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.