KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells

Morphoregulatory roles in pancreatic islet development

V. Cirulli, L. Crisa, G. M. Beattie, M. I. Mally, A. D. Lopez, A. Fannon, A. Ptasznik, Luca A Inverardi, Camillo Ricordi, T. Deerinck, M. Ellisman, R. A. Reisfeld, A. Hayek

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Cell adhesion molecules (CAMs) are important mediators of cell-cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell-cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.

Original languageEnglish
Pages (from-to)1519-1534
Number of pages16
JournalJournal of Cell Biology
Volume140
Issue number6
DOIs
StatePublished - Mar 23 1998

Fingerprint

Islets of Langerhans
Cell Adhesion
Epithelial Cells
Antigens
Pancreas
Glycoproteins
Epithelium
Growth
Epithelial Cell Adhesion Molecule
Cell Adhesion Molecules
Human Development
Glucagon
Nude Mice
Cell Communication
Fluorescent Antibody Technique
Cell Differentiation
Up-Regulation
Down-Regulation
Insulin
Calcium

ASJC Scopus subject areas

  • Cell Biology

Cite this

KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells : Morphoregulatory roles in pancreatic islet development. / Cirulli, V.; Crisa, L.; Beattie, G. M.; Mally, M. I.; Lopez, A. D.; Fannon, A.; Ptasznik, A.; Inverardi, Luca A; Ricordi, Camillo; Deerinck, T.; Ellisman, M.; Reisfeld, R. A.; Hayek, A.

In: Journal of Cell Biology, Vol. 140, No. 6, 23.03.1998, p. 1519-1534.

Research output: Contribution to journalArticle

Cirulli, V, Crisa, L, Beattie, GM, Mally, MI, Lopez, AD, Fannon, A, Ptasznik, A, Inverardi, LA, Ricordi, C, Deerinck, T, Ellisman, M, Reisfeld, RA & Hayek, A 1998, 'KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: Morphoregulatory roles in pancreatic islet development', Journal of Cell Biology, vol. 140, no. 6, pp. 1519-1534. https://doi.org/10.1083/jcb.140.6.1519
Cirulli, V. ; Crisa, L. ; Beattie, G. M. ; Mally, M. I. ; Lopez, A. D. ; Fannon, A. ; Ptasznik, A. ; Inverardi, Luca A ; Ricordi, Camillo ; Deerinck, T. ; Ellisman, M. ; Reisfeld, R. A. ; Hayek, A. / KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells : Morphoregulatory roles in pancreatic islet development. In: Journal of Cell Biology. 1998 ; Vol. 140, No. 6. pp. 1519-1534.
@article{62aa5d4f94d849848921095c3e31d4a6,
title = "KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: Morphoregulatory roles in pancreatic islet development",
abstract = "Cell adhesion molecules (CAMs) are important mediators of cell-cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell-cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.",
author = "V. Cirulli and L. Crisa and Beattie, {G. M.} and Mally, {M. I.} and Lopez, {A. D.} and A. Fannon and A. Ptasznik and Inverardi, {Luca A} and Camillo Ricordi and T. Deerinck and M. Ellisman and Reisfeld, {R. A.} and A. Hayek",
year = "1998",
month = "3",
day = "23",
doi = "10.1083/jcb.140.6.1519",
language = "English",
volume = "140",
pages = "1519--1534",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells

T2 - Morphoregulatory roles in pancreatic islet development

AU - Cirulli, V.

AU - Crisa, L.

AU - Beattie, G. M.

AU - Mally, M. I.

AU - Lopez, A. D.

AU - Fannon, A.

AU - Ptasznik, A.

AU - Inverardi, Luca A

AU - Ricordi, Camillo

AU - Deerinck, T.

AU - Ellisman, M.

AU - Reisfeld, R. A.

AU - Hayek, A.

PY - 1998/3/23

Y1 - 1998/3/23

N2 - Cell adhesion molecules (CAMs) are important mediators of cell-cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell-cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.

AB - Cell adhesion molecules (CAMs) are important mediators of cell-cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell-cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.

UR - http://www.scopus.com/inward/record.url?scp=0032559827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032559827&partnerID=8YFLogxK

U2 - 10.1083/jcb.140.6.1519

DO - 10.1083/jcb.140.6.1519

M3 - Article

VL - 140

SP - 1519

EP - 1534

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -