deregulation of the ceacam expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells放松管制的ceacam表达式模式导致人类肺腺癌细胞未分化的细胞生长.pdfVIP

Deregulation of the CEACAM Expression Pattern Causes Undifferentiated Cell Growth in Human Lung Adenocarcinoma Cells 1 1 2 3 1 Bernhard B. Singer *, Inka Scheffrahn , Robert Kammerer , Norbert Suttorp , Suleyman Ergun , Hortense Slevogt3 1 Institute of Anatomy, University Hospital Essen, Essen, Germany, 2 Institute of Immunology, Friedrich Loeffler Institute, Tuebingen, Germany, 3 Department of Internal ´ ¨ Medicine/Infectious Diseases and Pulmonary Medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany Abstract CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact- inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the i