Axl receptor tyrosine kinase expression in human lung cancer cell lines correlates with cellular adhesion.
Axl is a receptor tyrosine kinase (RTK) with oncogenic potential and transforming activity. Since Axl bears structural similarities to cell adhesion molecules such as neural cell adhesion molecule (NCAM) (FNIII domains), it is thought that Axl might play a role in adhesion. In this study, we have analysed the expression of the Axl protein and its ligand, Gas6, in human lung cancer cell lines of different histological origin. Axl expression occurred in approximately 60% of non-small cell lung cancer (NSCLC) cell lines, which grow adherently, and in normal bronchial epithelial cells (NHBE), but not in cell lines of small cell lung cancer origin (SCLC), which grow in suspension. A number of SCLC sublines, which could be selected spontaneously or after oncogene transfection for adherent growth, all expressed Axl protein. Overexpression of Axl per se, however, did not induce any change in the adhesion phenotype. All Axl-expressing cell lines demonstrated a membrane-bound 140 kD form, as well as a soluble 85 kD form, detectable in supernatant, of Axl-RTK. Expression of the Axl ligand Gas6 was detected in approximately 80% of all cell lines investigated. We conclude from these data that loss of Axl expression is a feature of SCLC tumour cells. Axl expression appears to be a consequence of cellular adhesion and possibly influences differentiation in human lung cancers.
Wimmel
A
A
Klinik für Innere Medizin, Sp. Hämatologie, Klinikum der Philipps-Universität, Baldinger Str., D-35033 Marburg, Germany.
Glitz
D
D
Kraus
A
A
Roeder
J
J
Schuermann
M
M
D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015513:Oncogene Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722289:AXL protein, human