TY - JOUR
T1 - Vacuolar apical compartment (VAC) in breast carcinoma cell lines (MCF-7 and T47D)
T2 - failure of the cell-cell regulated exocytosis mechanism of apical membrane
AU - Vega-Salas, Dora E.
AU - San Martino, Julio A.
AU - Salas, Pedro J.I.
AU - Baldi, Alberto
N1 - Funding Information:
Acknowledgement. The authors are grateful to Dr. L. Lustig, R. Ponzio and A. Solari (Fac. de Medicina, U.B.A.), for allowing us the use of the epifluorescence microscope; Dr. J. La Torre (Ctr. Virologia Animal, CONICET), for permitting us the access to the EM facility; Dr. A. De Nicola (IBYME) for proof reading the manuscript; Dr. J. Russo (Michigan Cancer Foundation, Detroit, USA) for providing us the MCF-10A cell line; and to Mrs. Zory Iglesias and Mrs. Nyanza Urivazo for typing the manuscript. Supported by grants from CONICET (3-147800 and PID-00183/89), UBA and Fundacion Antorchas. D.E. Vega-Salas, P.J.I. Salas and A. Baldi were career investigators from CONTCET. The authors dedicate this work in the memory of the admired scientist and Nobel awardee Dr. Luis F. Leloir, on the anniversary of his passing away.
PY - 1993
Y1 - 1993
N2 - We have previously shown that an integral plasma membrane glycoprotein (AP2) is highly polarized to the apical domain in confluent Madin-Darby canine kidney (MDCK) epithelial cells. However, when the monolayers are prevented from forming intercellular contacts, approximately 60% of the AP2 cellular content is stored in the intracellular vacuolar apical compartment (VAC). In the current work we found that AP2 was present in the non-tumorigenic human mammary epithelial cell line MCF-10A, in the breast carcinoma cell lines MCF-7 and T47D, and in breast ductal carcinomas in vivo. By radioimmunoassay, an intracellular compartment of AP2 was identified in the mammary cell lines in culture. In MCF-10A, this compartment behaved as in MDCK cells; namely it was observed only when the cells cannot form cell-cell contacts. However, in the carcinoma cell lines MCF-7 and T47D, a significant AP2 intracellular compartment was observed also under conditions permissive for the formation of intercellular contacts. These results were confirmed by immunofluorescence and immunoelectron microscopy experiments that showed VACs in MCF-7 and T47D, even in cells with extensive intercellular contacts. In MCF-7 cells, the addition of serum caused a partial decrease of the AP2 intracellular compartment. The exocytosis of VACs occurred towards the center of multi-cellular groups, forming intercellular lumens, similar to those transiently observed in MDCK cells and to structures described by others during embryo development. Altogether, these results suggest that VAC exocytosis is controlled by cell-cell contact signalling, which may be defective in carcinoma cells.
AB - We have previously shown that an integral plasma membrane glycoprotein (AP2) is highly polarized to the apical domain in confluent Madin-Darby canine kidney (MDCK) epithelial cells. However, when the monolayers are prevented from forming intercellular contacts, approximately 60% of the AP2 cellular content is stored in the intracellular vacuolar apical compartment (VAC). In the current work we found that AP2 was present in the non-tumorigenic human mammary epithelial cell line MCF-10A, in the breast carcinoma cell lines MCF-7 and T47D, and in breast ductal carcinomas in vivo. By radioimmunoassay, an intracellular compartment of AP2 was identified in the mammary cell lines in culture. In MCF-10A, this compartment behaved as in MDCK cells; namely it was observed only when the cells cannot form cell-cell contacts. However, in the carcinoma cell lines MCF-7 and T47D, a significant AP2 intracellular compartment was observed also under conditions permissive for the formation of intercellular contacts. These results were confirmed by immunofluorescence and immunoelectron microscopy experiments that showed VACs in MCF-7 and T47D, even in cells with extensive intercellular contacts. In MCF-7 cells, the addition of serum caused a partial decrease of the AP2 intracellular compartment. The exocytosis of VACs occurred towards the center of multi-cellular groups, forming intercellular lumens, similar to those transiently observed in MDCK cells and to structures described by others during embryo development. Altogether, these results suggest that VAC exocytosis is controlled by cell-cell contact signalling, which may be defective in carcinoma cells.
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U2 - 10.1111/j.1432-0436.1993.tb01596.x
DO - 10.1111/j.1432-0436.1993.tb01596.x
M3 - Article
C2 - 8243890
AN - SCOPUS:0027380783
VL - 54
SP - 131
EP - 141
JO - Differentiation
JF - Differentiation
SN - 0301-4681
IS - 3
ER -