Journal Mobile Options
Table of Contents
Vol. 26, No. 4, 2005
Issue release date: July–August 2005
Tumor Biol 2005;26:195–200

Enhanced Expression of Aggrus (T1alpha/Podoplanin), a Platelet-Aggregation-Inducing Factor in Lung Squamous Cell Carcinoma

Kato Y. · Kaneko M. · Sata M. · Fujita N. · Tsuruo T. · Osawa M.
aDepartment of Experimental and Forensic Pathology and bFirst Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, and cInstitute of Molecular and Cellular Biosciences, University of Tokyo, and dCancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Aggrus (T1α/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Travis WD, Travis LB, Devesa SS: Lung cancer. Cancer 1995;75:191–202.
  2. Tsuruo T, Yamori T, Naganuma K, Tsukagoshi S, Sakurai Y: Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26. Cancer Res 1983;43:5437–5442.
  3. Watanabe M, Okochi E, Sugimoto Y, Tsuruo T: Identification of a platelet-aggregating factor of murine colon adenocarcinoma 26: Mr 44,000 membrane protein as determined by monoclonal antibodies. Cancer Res 1988;48:6411–6416.
  4. Sugimoto Y, Watanabe M, Oh-hara T, Sato S, Isoe T, Tsuruo T: Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8F11 inhibiting tumor cell-induced platelet aggregation. Cancer Res 1991;51:921–925.
  5. Kato Y, Fujita N, Kunita A, Sato S, Kaneko M, Osawa M, Tsuruo T: Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. J Biol Chem 2003;278:51599–51605.
  6. Boucherot A, Schreiber R, Pavenstadt H, Kunzelmann K: Cloning and expression of the mouse glomerular podoplanin homologue gp38P. Nephrol Dial Transplant 2002;17:978–984.
  7. Nose K, Saito H, Kuroki T: Isolation of a gene sequence induced later by tumor-promot ing 12-O-tetradecanoylphorbol-13-acetate in mouse osteoblastic cells (MC3T3-E1) and expressed constitutively in ras-transformed cells. Cell Growth Differ 1990;1:511–518.
  8. Ma T, Yang B, Matthay MA, Verkman AS: Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels. Am J Respir Cell Mol Biol 1998;19:143–149.
  9. Kato Y, Sasagawa I, Kaneko M, Osawa M, Fujita N, Tsuruo T: Aggrus: A diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors. Oncogene 2004;23:8552–8556.
  10. Wetterwald A, Hoffstetter W, Cecchini MG, Lanske B, Wagner C, Fleisch H, Atkinson M: Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. Bone 1996;18:125–132.
  11. Rishi AK, Joyce-Brady M, Fisher J, Dobbs LG, Floros J, VanderSpek J, Brody JS, Williams MC: Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives. Dev Biol 1995;167:294–306.
  12. Williams MC, Cao Y, Hinds A, Rishi AK, Wetterwald A: T1 alpha protein is developmentally regulated and expressed by alveolar type I cells, choroid plexus, and ciliary epithelia of adult rats. Am J Respir Cell Mol Biol 1996;14:577–585.
  13. Scholl FG, Gamallo C, Vilaró S, Quintanilla M: Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci 1999;112:4601–4613.
  14. Ramirez MI, Millien G, Hinds A, Cao Y, Seldin DC, Williams MC: T1alpha, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth. Dev Biol 2003;256:61–72.
  15. Kaneko M, Kato Y, Kunita A, Fujita N, Tsuruo T, Osawa M: Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. J Biol Chem 2004;279:38838–38843.
  16. Toyoshima M, Nakajima M, Yamori T, Tsuruo T: Purification and characterization of the platelet-aggregating sialoglycoprotein gp44 expressed by highly metastatic variant cells of mouse colon adenocarcinoma 26. Cancer Res 1995;55:767–773.
  17. Kawai K, Sasaki T, Saijo-Kurita K, Akaza H, Koiso K, Ohno T: Additive effects of antitumor drugs and lymphokine-activated killer cell cytotoxic activity in tumor cell killing determined by lactate-dehydrogenase-release assay. Cancer Immunol Immunother 1992;35:225–229.
  18. Tsuruta N, Yatsunami J, Takayama K, Nakanishi Y, Ichinose Y, Hara N: Granulocyte-macrophage-colony stimulating factor stimulates tumor invasiveness in squamous cell lung carcinoma. Cancer 1998;82:2173–2183.
  19. Yamori T, Matsunaga A, Sato S, Yamazaki K, Komi A, Ishizu K, Mita I, Edatsugi H, Matsuba Y, Takezawa K, Nakanishi O, Kohno H, Nakajima Y, Komatsu H, Andoh T, Tsuruo T: Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel. Cancer Res 1999;59:4042–4049.
  20. Nakashio A, Fujita N, Rokudai S, Sato S, Tsuruo T: Prevention of phosphatidylinositol 3′-kinase-Akt survival signaling pathway during topotecan-induced apoptosis. Cancer Res 2000;60:5303–5309.
  21. Broers JL, Ramaekers FC, Rot MK, Oostendorp T, Huysmans A, van Muijen GN, Wagenaar SS, Vooijs GP: Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies. Cancer Res 1988;48:3221–3229.
  22. Sculier JP, Body JJ, Jacobowitz D, Fruhling J: Value of CEA determination in biological fluids and tissues. Eur J Cancer Clin Oncol 1987;23:1091–1093.
  23. Body JJ, Sculier JP, Raymakers N, Paesmans M, Ravez P, Libert P, Richez M, Dabouis G, Lacroix H, Bureau G, Thiriaux J, Lecomte J, Brohee D, Mommen P, Fruhling J, Klastersky J: Evaluation of squamous cell carcinoma antigen as a new marker for lung cancer. Cancer 1990;65:1552–1556.
  24. Rastel D, Ramaioli A, Cornillie F, Thirion B: CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung cancer. Report of the first European multicentre evaluation. CYFRA 21-1 Multicentre Study Group. Eur J Cancer 1994;30:601–606.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50