Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or OpenAthens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Interleukin-15 Expression Is Associated with Malignant Potential in Colon Cancer Cells

Kuniyasu H.a · Oue N.b · Nakae D.a · Tsutsumi M.a · Denda A.a · Tsujiuchi T.a · Yokozaki H.b · Yasui W.b

Author affiliations

aDepartment of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, and bFirst Department of Pathology, Hiroshima University School of Medicine, Hiroshima, Japan

Related Articles for ""

Pathobiology 2001;69:86–95

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





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

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: December 14, 2001
Issue release date: December 2001

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 2

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: https://www.karger.com/PAT

Abstract

Interleukin 15 (IL-15 mRNA expression was detected in human colorectal cancer cells (Colo320, WiDr, TCO and DLD1) by the reverse transcriptase-polymerase chain reaction (RT-PCR). Only Colo320 and WiDr cells secreted IL-15 culture medium. With IL-15 treatment, all cell lines grew at a rate of 120–180% of that of nontreated cells. A binding assay with 125I-labeled IL-15 showed binding activity to IL-15 in Colo320 (Kd: 0.098 nM) cells. IL-15 also reversed the growth inhibition caused by serum starvation in Colo320 cells. IL-15-induced cell growth in regular and serum-free media was abrogated by anti-IL-15 antibody treatment in Colo320 cells. Moreover, IL-15 treatment reduced doxorubicin-induced cytostasis and cytolysis in Colo320 cells by 50%. The invasion capacity of IL-15-treated Colo320 cells was 5.3 times that of untreated cells. Immunoblotting showed that IL-15-treated Colo320 cells exhibited downregulation of p21Waf1 and Bax, and upregulation of Bcl-2, phospho-AKT, MMP9/MMP2, and VEGF. Finally, immunostaining of human colon cancer revealed that 33 (70%) of 47 Dukes’ C cases showed IL-15 expression in cancer cells, whereas only 16% of Dukes’ B cases did (p < 0.0001). IL-15 may play important roles in cell proliferation, invasion, and metastasis of human colorectal cancer.

© 2001 S. Karger AG, Basel


References

  1. Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai CF, et al: A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest 1997;99:937–943.
  2. Allavena P, Giardina G, Bianchi G, Mantovani A: IL-15 is chemotactic for natural killer cells and stimulates their adhesion to vascular endothelium. J Leukoc Biol 1997;61:729–735.
    External Resources
  3. Waldmann T, Tagaya Y, Bamford R: Interleukin-2, interleukin-15, and their receptors. Int Rev Immunol 1998;16:205–226.
  4. Bulfone-Paus S, Ungureanu D, Pohl T, Lindner G, Paus R, Ruckert R, et al: Interleukin-15 protects from lethal apoptosis in vivo. Nat Med 1997;3:1124–1128.
  5. Angiolillo AL, Kanegane H, Sgadari C, Reaman GH, Tosato G: Interleukin-15 promotes angiogenesis in vivo. Biochem Biophys Res Commun 1997;233:231–237.
  6. Adunyah SE, Wheeler BJ, Cooper RS: Evidence for the involvement of LCK and MAP kinase (ERK-1) in the signal transduction mechanism of interleukin-15. Biochem Biophys Res Commun 1997;232:754–758.
  7. Podolsky DK: Healing the epithelium: Solving the problem from two sides. J Gastroenterol 1997;32:122–126.
  8. Reinecker HC, MacDermott RP, Mirau S, Dignass A, Podolsky DK: Intestinal epithelial cells both express and respond to interleukin-15. Gastroenterology 1996;111:1706–1713.
  9. Inagaki-Ohara K, Nishimura H, Mitani A, Yoshikai Y: Interleukin-15 preferentially promotes the growth of intestinal intraepithelial lymphocytes bearing gamma delta T cell receptor in mice. Eur J Immunol 1997;27:2885–2891.
  10. Nishimura Y, Yasui W, Yoshida K, Matsuyama T, Dohi K, Tahara E: A serine protease-inhibitory benzamidine derivative inhibits the growth of human colon carcinoma cells. Jpn J Cancer Res 1992;83:723–728.
  11. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, et al: Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 1988;48:589–601.
  12. Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Ito H, et al: Expression of epidermal growth factor receptor in human gastric and colonic carcinoma. Cancer Res 1988;48:211–217.
  13. Podolsky DK: Lessons from genetic models of inflammatory bowel disease. Acta Gastroenterol Belg 1997;60:163–165.
  14. Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM: Serine/threonine protein kinases and apoptosis. Exp Cell Res 2000;256:34–41.
  15. Gross A, McDonnell JM, Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899–1911.
  16. Tsujimoto Y: Role of Bcl-2 family proteins in apoptosis: Apoptosomes or mitochondria? Genes Cells 1998;3:697–707.
  17. Tsujimoto Y, Shimizu S: Bcl-2 family: Life-or-death switch. FEBS Lett 2000;466:6–10.
  18. Shimizu S, Konishi A, Kodama T, Tsujimoto Y: BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc Natl Acad Sci USA 2000;97:3100–3105.
  19. Coffer PJ, Jin J, Woodgett JR: Protein kinase B (c-Akt): A multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J 1998;335:1–13.
  20. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G: Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 1997;278:687–689.
  21. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997;91:231–241.
  22. Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, et al: Regulation of cell death protease caspase-9 by phosphorylation. Science 1998;282:1318–1321.
  23. Kennedy SG, Kandel ES, Cross TK, Hay N: Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol 1999;19:5800–5810.
  24. Madrid LV, Wang CY, Guttridge DC, Schottelius AJ, Baldwin AS Jr, Mayo MW: Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol Cell Biol 2000;20:1626–1638.
  25. Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999;401:86–90.
  26. Matsuzaki H, Tamatani M, Mitsuda N, Namikawa K, Kiyama H, Miyake S, et al: Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. J Neurochem 1999;73:2037–2046.
  27. Demoulin JB, Renauld JC: Signalling by cytokines interacting with the interleukin-2 receptor gamma chain. Cytokines Cell Mol Ther 1998;4:243–256.
  28. Gomez J, Gonzalez A, Martinez AC, Rebollo A: IL-2-induced cellular events. Crit Rev Immunol 1998;18:185–220.
    External Resources
  29. Tagaya Y, Bamford RN, DeFilippis AP, Waldmann TA: IL-15: A pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. Immunity 1996;4:329–336.
  30. Finlay D, Healy V, Furlong F, O’Connell FC, Keon NK, Martin F: MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival. Cell Death Differ 2000;7:302–313.
  31. Reddy KB, Krueger JS, Kondapaka SB, Diglio CA: Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int J Cancer 1999;82:268–273.
  32. Westermarck J, Kahari VM: Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999;13:781–792.
  33. Matsumoto K, Kanmatsuse K: Interleukin-15 and interleukin-12 have an additive effect on the release of vascular permeability factor by peripheral blood mononuclear cells in normals and in patients with nephrotic syndrome. Clin Nephrol 1999;52:10–18.
    External Resources
  34. Badolato R, Ponzi AN, Millesimo M, Notarangelo LD, Musso T: Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes. Blood 1997;90:2804–2809.
  35. McDonald PP, Russo MP, Ferrini S, Cassatella MA: Interleukin-15 (IL-15) induces NF-kappaB activation and IL-8 production in human neutrophils. Blood 1998;92:4828–4835.
  36. Lugering N, Kucharzik T, Maaser C, Kraft M, Domschke W: Interleukin-15 strongly inhibits interleukin-8 and monocyte chemoattractant protein-1 production in human colonic epithelial cells. Immunology 1999;98:504–509.
    External Resources
  37. Carson WE, Giri JG, Lindemann MJ, Linett ML, Ahdieh M, Paxton R, et al: Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 1994;180:1395–1403.
  38. Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, et al: Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 1995;95:2945–2953.
  39. Maeurer MJ, Walter W, Martin D, Zitvogel L, Elder E, Storkus W, et al: Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes. Scand J Immunol 1997;45:182–192.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: December 14, 2001
Issue release date: December 2001

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 2

ISSN: 1015-2008 (Print)
eISSN: 1423-0291 (Online)

For additional information: https://www.karger.com/PAT


Copyright / Drug Dosage / Disclaimer

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.
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 government 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.