Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
      • Neuroimmunology: To Sense and Protect
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice

Erika Cretney, Kazuyoshi Takeda, Hideo Yagita, Moira Glaccum, Jacques J. Peschon and Mark J. Smyth
J Immunol February 1, 2002, 168 (3) 1356-1361; DOI: https://doi.org/10.4049/jimmunol.168.3.1356
Erika Cretney
*Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuyoshi Takeda
†Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hideo Yagita
†Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Moira Glaccum
‡Immunex Corporation, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacques J. Peschon
‡Immunex Corporation, Seattle, WA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J. Smyth
*Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • FIGURE 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 1.

    Absence of TRAIL expression in TRAIL gene-targeted mice. Liver MNC were isolated from WT or TRAIL−/− B6 mice and were stained with FITC-conjugated anti-CD3 mAb, PE-conjugated anti-TRAIL mAb, and biotin-conjugated anti-NK1.1 mAb followed by streptavidin-PerCP. A and C, NK1.1/CD3 staining of WT and TRAIL−/− mice, respectively, with R2 representing the gated NK cell population. B, TRAIL expression on WT liver NK cells (R2 gated). D, Absence of TRAIL on TRAIL−/− liver NK cells (R2 gated). Solid lines represent staining with isotype-matched control mAb; dotted lines represent staining with anti-mouse TRAIL mAb. These analyses have been performed on more than three occasions and these profiles are representative.

  • FIGURE 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 2.

    TRAIL gene-targeted mice do not exert TRAIL-mediated cytotoxicity. Liver and spleen MNC were isolated from untreated BALB/c WT, BALB/c pfp−/−, BALB/c IFN-γ−/−, or BALB/c TRAIL−/− mice (A and B), and liver MNC were isolated from α-GalCer (2 μg i.p. on days −5 and −1)-treated BALB/c WT or BALB/c TRAIL−/− mice (C). Their cytotoxic activities were tested against TRAIL-sensitive 4T1 (A and C) and Renca (B and C) tumor cells in the presence or absence of 50 nM CMA, 10 μg/ml anti-TRAIL mAb, or 10 μg/ml control rat IgG2a (control) by an 8-h 51Cr release assay at three different E:T ratios (highest, 100:1 for spleen MNC; highest, 50:1 for liver MNC, shown) as indicated. Data are representative of those across the E:T ratio range (100 to 5:1, spleen; 50 to 5:1, liver) and are recorded as the mean ± SE of triplicate samples. Similar results were obtained in two independent experiments.

  • FIGURE 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 3.

    TRAIL contributes to NK cell suppression of experimental Renca metastases to the liver. Groups of WT or TRAIL−/− BALB/c mice were inoculated i.s. with Renca tumor cells ranging from 1 × 104–3 × 105 (A), i.s. with 3 × 105 Renca tumor cells (B), or i.v. with 3 × 105 Renca tumor cells (C) on day 0. As indicated, some groups of mice were treated with 200 μg of anti-asGM1 Ab i.p. on days −1, 0, and 7 (A–C), 0.25 mg of anti-TRAIL mAb i.p. on days 0, 1, and 7 (A–C), and 2 μg of α-GalCer i.p. on days 0, 4, and 8 (B and C). The livers (A and B) or lungs (C) were removed from mice on day 14, and the metastatic nodules were quantified as described in Materials and Methods. Data are indicated as the mean ± SE of five mice in each group, with the significance compared with untreated (A) or α-GalCer-treated (B and C) WT mice as defined by the Mann-Whitney U test. ∗, p < 0.01; ∗∗, p < 0.05. α-GalCer was also statistically effective alone compared with no treatment in the livers and lungs of WT mice (p < 0.01). We have previously shown no significant effects of rabbit and mouse control Igs in these models (14 ).

  • FIGURE 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 4.

    TRAIL contributes to the suppression of primary 4T1 tumor growth and spontaneous metastasis. A–C, Groups of female BALB/c WT or TRAIL−/− mice were inoculated on day 0 into the abdominal mammary fat pad with 5 × 103 (A), 1 × 104 (B), or 2.5 × 104 (C) 4T1 mammary carcinoma cells. Some groups of mice were treated with 200 μg of anti-asGM1 Ab i.p. on days −1, 0, 7, and 14, or 0.25 mg of anti-TRAIL mAb i.p. on days 0, 1, 4, 7, 10, 14, and 21. Tumor size was measured over the course of 30 days. Data are shown as the mean ± SE of five tumor-bearing mice in each group. D–F, Groups of female BALB/c WT or TRAIL−/− mice were inoculated on day 0 into the abdominal mammary fat pad with 2.5 × 104 4T1 mammary carcinoma cells and were i.p. administered with 2 μg of α-GalCer on days 0, 4, 8, 12, and 16. Some groups of mice were treated with 200 μg of anti-asGM1 Ab i.p. on days −1, 0, 7, and 14 or 0.25 mg of anti-TRAIL mAb i.p. on days 0, 1, 4, 7, 10, 14, and 21. Primary tumor growth in the mammary gland was measured over the course of 30 days (D). Lung metastases (E) and liver metastases (F) were measured as described in Materials and Methods. Data are indicated as the mean ± SE of five mice in each group, with the significance compared with α-GalCer-treated WT mice as defined by the Mann-Whitney U test. ∗, p < 0.01. α-GalCer was also statistically effective alone compared with no treatment in the livers and lungs of WT mice (p < 0.01).

  • FIGURE 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 5.

    TRAIL suppresses MCA induction of fibrosarcomas. Groups of 10–30 B6 WT (▪) or TRAIL−/− (□) mice were inoculated s.c. in the hind flank with 400, 100, 25, or 5 μg of MCA in 0.1 ml of corn oil. Development of sarcomas was monitored over the course of 80–160 days, and the percentage of mice with sarcoma was recorded. ∗, Statistically increased sarcoma incidence above that observed in WT (Fisher’s exact test, p < 0.05).

PreviousNext
Back to top

In this issue

The Journal of Immunology: 168 (3)
The Journal of Immunology
Vol. 168, Issue 3
1 Feb 2002
  • Table of Contents
  • About the Cover
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice
Erika Cretney, Kazuyoshi Takeda, Hideo Yagita, Moira Glaccum, Jacques J. Peschon, Mark J. Smyth
The Journal of Immunology February 1, 2002, 168 (3) 1356-1361; DOI: 10.4049/jimmunol.168.3.1356

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice
Erika Cretney, Kazuyoshi Takeda, Hideo Yagita, Moira Glaccum, Jacques J. Peschon, Mark J. Smyth
The Journal of Immunology February 1, 2002, 168 (3) 1356-1361; DOI: 10.4049/jimmunol.168.3.1356
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Early Self-Regulatory Mechanisms Control the Magnitude of CD8+ T Cell Responses Against Liver Stages of Murine Malaria
  • Sublethal Hyperoxia Impairs Pulmonary Innate Immunity
  • Dependence of IL-4, IL-13, and Nematode-Induced Alterations in Murine Small Intestinal Smooth Muscle Contractility on Stat6 and Enteric Nerves
Show more HOST DEFENSE

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2021 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606