Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Metabolism Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Spotlight on Genomic Analysis of Rare and Understudied Cancers
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Research
Molecular Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Metabolism Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Spotlight on Genomic Analysis of Rare and Understudied Cancers
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Signal Transduction and Functional Imaging

A Hypoxia-Inducible HIF1–GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell–Platelet Binding

Claire M. Robinson, Betty P.K. Poon, Yoshihito Kano, Fred G. Pluthero, Walter H.A. Kahr and Michael Ohh
Claire M. Robinson
1Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
2Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Betty P.K. Poon
1Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
2Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshihito Kano
1Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
2Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yoshihito Kano
Fred G. Pluthero
3Division of Haematology/Oncology and Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Fred G. Pluthero
Walter H.A. Kahr
2Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
3Division of Haematology/Oncology and Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada.
4Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Ohh
1Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
2Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: michael.ohh@utoronto.ca
DOI: 10.1158/1541-7786.MCR-19-0461 Published November 2019
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    GAL3ST1 expression is upregulated in ccRCC. Patients were separated into two groups based on FPKM value for GAL3ST1. Kaplan–Meier estimator measured survival outcomes in patients expressing high or low GAL3ST1 mRNA and outcomes of the two groups were compared with log-rank tests [log-rank P = 1.79e-4 (prognostic, unfavorable)].

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

    Sulfatides promote platelet binding to cancer cells. A, Wells of a 96-well plate were coated with 2 μg/mL BSA or bovine sulfatides. Washed human platelets from healthy donors were stained with calcein AM and incubated in the coated wells. Following washes, florescence was measured using a fluorescent plate reader. Results are presented as a percent change in fluorescence of control (BSA). Data were analyzed using unpaired Student t test where, ***, P < 0.001. B, 786-shSCR and 786-shGAL were coincubated with human platelets from healthy donors stained with wheat germ agglutinin (red). Actin (green) stained both cells and activated platelets, while nuclei were stained with Hoechst (blue). C, An example of flow cytometry data acquired demonstrating the emergence of a double-positive cell population. Platelets were coincubated with GFP+ renal cancer cells for 5 minutes. Samples were fixed, stained with PE-CD41, and analyzed using flow cytometry. D, The percentage of a GFP+ PE-CD41+ population was graphed for each platelet donor tested (n = 3).

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

    Platelets protect GAL3ST1-sulfatide–expressing cells from NK cell–mediated destruction but not GAL3ST1-sulfatide–negative cells. NK-92 cells were stained with Calcein-Red. 786-shSCR or -shGAL3ST1 are GFP+. Cancer cells were incubated for 3 hours in the presence or absence of NK-92 cells ± washed healthy platelets. After incubations, cells were stained for 7-AAD and Annexin V and cell death was quantified using flow cytometry. A, An example of the gating regime applied to the experiments presented and the significant shift in AnnexinV+ cells upon coincubation of ccRCC cells with NK-92 cells. A total of 10,000 events were recorded for each experiment. B, Cell death in 786-shSCR and 786-shGAL3ST1 cells coincubated in the presence or absence of platelets (P) or NK-92 cells (NK). Untreated cancer cells are presented in the figure as NT. n = 5 with washed human platelets from 5 healthy donors. C, NK-mediated cell death in samples coincubated with platelets in 786-shSCR and 786-shGAL3ST1 cells. A paired t test was used to evaluate significance between the groups where n = 5 healthy donors. D, Using the same experimental setup, platelets were activated with U46619 and then coincubated with shSCR or shGAL3ST1 ± NK-92 cells. In figures B and D, a one-way ANOVA with post hoc Tukey test was applied to determine statistical significance (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant).

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

    Model of GAL3ST1 in NK cell–mediated tumor cell killing. VHL−/− renal cancer cells express high levels of GAL3ST1 and NK cells can target these cells for destruction (left). In the presence of platelets that interact with VHL−/− cells, NK cells have significantly restricted abilities to target renal cancer cells for destruction (middle). When GAL3ST1 expression is decreased, platelet interactions with renal cancer cells are perturbed and NK-mediated killing is increased (right).

Tables

  • Figures
  • Additional Files
  • Table 1.

    A list of the most upregulated genes in 10 ccRCC samples compared with normal kidney

    RankGene IDGene symbol
    154901NDUFA4L2
    284634KISS1R
    37130TNFAIP6
    44885NPTX2
    51573CYP2J2
    62173FABP7
    751129ANGPTL4
    8112399EGLN3
    9100133188NA
    105169ENPP3
    ...............
    421520CTSS
    439514GAL3ST1
    44714C1QC
    • NOTE: Gene expression in 10 primary ccRCC tumor samples was analyzed by Affymetrix microarray; GEO accession #GDS1344. Averages were measured across all 10 samples and ranked from highest to lowest (see top 50 list in Table 2.1 in ref. 14).

Additional Files

  • Figures
  • Tables
  • Supplementary Data

    • Supplementary Data - Microarray expression data
    • Supplementary Figure 1 - S1. ChIP Atlas was used to interrogate HIF1, EPAS and ARNT binding at the GAL3ST1 locus using ChIP-seq data from various kidney (cancerous and healthy) cells
    • Supplementary Figure 2 - S2. RCC4 ChIP -seq data (GEO accession #GSE120885) for HIF1 and HIF2 at GAL3ST1 promoter, including regions 'HRE1' and 'HRE2'.
PreviousNext
Back to top
Molecular Cancer Research: 17 (11)
November 2019
Volume 17, Issue 11
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A Hypoxia-Inducible HIF1–GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell–Platelet Binding
(Your Name) has forwarded a page to you from Molecular Cancer Research
(Your Name) thought you would be interested in this article in Molecular Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
A Hypoxia-Inducible HIF1–GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell–Platelet Binding
Claire M. Robinson, Betty P.K. Poon, Yoshihito Kano, Fred G. Pluthero, Walter H.A. Kahr and Michael Ohh
Mol Cancer Res November 1 2019 (17) (11) 2306-2314; DOI: 10.1158/1541-7786.MCR-19-0461

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
A Hypoxia-Inducible HIF1–GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell–Platelet Binding
Claire M. Robinson, Betty P.K. Poon, Yoshihito Kano, Fred G. Pluthero, Walter H.A. Kahr and Michael Ohh
Mol Cancer Res November 1 2019 (17) (11) 2306-2314; DOI: 10.1158/1541-7786.MCR-19-0461
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of Resistance to Dasatinib in KIT-Altered Melanoma
  • BRAF-Mutant Melanoma Depends on ERK2
  • The CLDN6/ERα Axis in Endometrial Cancer
Show more Signal Transduction and Functional Imaging
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Rapid Impact Archive
  • Meeting Abstracts

Information for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About MCR

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Molecular Cancer Research
eISSN: 1557-3125
ISSN: 1541-7786

Advertisement