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

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • 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

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Experimental and Molecular Therapeutics

Abstract 1601: COX-2 and EP4 receptor as targets to ameliorate tumor growth, lymphangiogenesis, and metastasis in a murine breast cancer model

Peeyush K. Lala, Vik Mohindra, Xiping Xin, Ling Liu and Gannareddy Girish
Peeyush K. Lala
1Univ. of Western Ontario, London, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vik Mohindra
1Univ. of Western Ontario, London, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiping Xin
1Univ. of Western Ontario, London, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ling Liu
1Univ. of Western Ontario, London, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gannareddy Girish
1Univ. of Western Ontario, London, Ontario, Canada.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM10-1601 Published April 2010
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Abstract

We had earlier shown that elevated cyclo-oxygenase (COX)-2 expression by breast cancer cells promotes tumor progression and metastasis by multiple mechanisms: inactivation of host immune cells, stimulation of tumor cell migration and tumor-associated angiogenesis. Furthermore, COX-2 was causally associated with increased VEGF-C expression/secretion in human breast cancer cell lines, corroborated with in situ studies on breast cancer tissue specimens, showing a strong correlation of COX-2 with VEGF-C and lymphangiogenic markers or lymphovascular density, implicated in lymphatic metastasis. VEGF-C upregulation resulted from PGE2-mediated stimulation of EP4, and to a smaller extent, EP1 receptors on breast cancer cells. Since human tumor xeno-transplants in immno-compromised hosts are less than ideal for a therapeutic testing of these findings, in the present study, we developed a syngeneic murine breast cancer model exhibiting lymphangiogenesis and lymphatic metastasis in C3H/HeJ mice, using a highly metastatic, COX-2 expressing C3L5 cell line. This cell line was found to express VEGF-C and VEGF-D mRNA and proteins, and all four EP receptors. Expression of VEGF-C and VEGF-D were suppressed by treatment of cells with COX-2 inhibitors or EP4 antagonist in vitro. C3L5 cells suspended in growth factor-reduced Matrigel were implanted in both inguinal regions in mice that received oral treatments with COX-1/2 inhibitor indomethacin, COX-2 inhibitor celecoxib, EP1 antagonist ONO-8713 or EP4 antagonist ONO-AE3-208, to evaluate tumor growth, metastasis to lymph nodes and the lungs and tumor-associated angiogenesis (CD31 immuno-staining) and lymphangiogenesis (LYVE1 immunostaining). Mice were killed on days 8, 12 and 16. Tumor growth in control vehicle-treated mice was associated with high levels of angiogenesis and lymphangiogenesis at all intervals. VEGF-C protein expression was noted in 20-30% of tumor cells as well as macrophages in situ. Micro-metastasis to the lungs and local lymph nodes was noted as early as day 8 and increased thereafter. Metastasis to distant axillary nodes was seen at day16. Significant reduction in tumor growth, tumor-associated angiogenesis and lymphangiogenesis, and metastasis to the lungs and lymph nodes was achieved by therapies with indomethacin, celecoxib and ONO-AE3-208 but not ONO-8713 as compared to respective vehicle treatments. In conclusion, we have devised a syngeneic mouse breast cancer model mimicking human, showing successful chemo-intervention of tumor growth, tumor-associated angiogenesis/lymphangiogenesis and metastasis to the lungs and lymph nodes with COX inhibitors and EP 4 antagonist. (Supported by grants from the Canadian Breast Cancer Foundation, Ontario chapter and the Ontario Institute of Cancer Research to PKL. EP antagonists were kindly provided by ONO pharmaceuticals, Japan and Celecoxib by Pfizer.)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1601.

  • ©2010 American Association for Cancer Research
Back to top
Cancer Research: 70 (8 Supplement)
April 2010
Volume 70, Issue 8 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this 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.
Abstract 1601: COX-2 and EP4 receptor as targets to ameliorate tumor growth, lymphangiogenesis, and metastasis in a murine breast cancer model
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract 1601: COX-2 and EP4 receptor as targets to ameliorate tumor growth, lymphangiogenesis, and metastasis in a murine breast cancer model
Peeyush K. Lala, Vik Mohindra, Xiping Xin, Ling Liu and Gannareddy Girish
Cancer Res April 15 2010 (70) (8 Supplement) 1601; DOI: 10.1158/1538-7445.AM10-1601

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 1601: COX-2 and EP4 receptor as targets to ameliorate tumor growth, lymphangiogenesis, and metastasis in a murine breast cancer model
Peeyush K. Lala, Vik Mohindra, Xiping Xin, Ling Liu and Gannareddy Girish
Cancer Res April 15 2010 (70) (8 Supplement) 1601; DOI: 10.1158/1538-7445.AM10-1601
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
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Experimental and Molecular Therapeutics

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - New Molecular Targets 4: Identification of Molecular Targets II

  • Abstract 1626: Tyrosine phosphorylation of RIN1 modulates the anti-proliferative effects of sorafenib and sunitinib in renal cell carcinoma (RCC)
  • Abstract 1624: Identification and characterization of phospho-ORM-1 as a novel nicotinic acetylcholine receptor (NAChR)-associated protein and a potential serum marker for lung cancer detection
  • Abstract 1625: Discovery of a breast cancer targeting peptide with anti-tumor activity
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

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

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement