Cancer Cell Biology
Characterization of human PA2.26 antigen (T1α–2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas
Article first published online: 28 OCT 2004
Copyright © 2004 Wiley-Liss, Inc.
International Journal of Cancer
Volume 113, Issue 6, pages 899–910, 1 March 2005
How to Cite
Martín-Villar, E., Scholl, F. G., Gamallo, C., Yurrita, M. M., Muñoz-Guerra, M., Cruces, J. and Quintanilla, M. (2005), Characterization of human PA2.26 antigen (T1α–2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. Int. J. Cancer, 113: 899–910. doi: 10.1002/ijc.20656
- Issue published online: 20 DEC 2004
- Article first published online: 28 OCT 2004
- Manuscript Accepted: 10 AUG 2004
- Manuscript Received: 3 MAR 2004
- Fondo de Investigaciones Sanitarias. Grant Numbers: FIS-01/1125, FIS-02/1025
- Ministerio de Ciencia y Tecnología. Grant Number: SAF2001-2361
- Fundación Carolina
We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1α-2, podoplanin), a small mucin-type transmembrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca2+-dependent cell-cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion. © 2004 Wiley-Liss, Inc.