• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2010 Fiscal Year Final Research Report

Critical role of TGF-beta for tumor angiogenic switch

Research Project

  • PDF
Project/Area Number 21791243
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionGunma University

Principal Investigator

FUJII Takaaki  Gunma University, 医学部, 助教 (40507331)

Project Period (FY) 2009 – 2010
Keywords腫瘍血管新生 / TGF-β / VEGF / FGF-2 / angiogenic switch / PDGF-AA
Research Abstract

Angiogenesis is required for tumor progression, as supported by a number of studies showing a reduction in tumor growth by antiangiogenic agent, including anti-VEGF (vascular endothelial growth factor) antibody. A shift of the angiogenic balance to the proangiogenic state, temrmed the 'angiogenic switch', is a hallmark of cancer progression. VEGF has been recognized as one of the most potent mediators of tumor angiogenesis. However, VEGF is not an angiogenic factor, because VEGF is abundantly expressed in not only cancers but also precancerous lesions and their originating tissue. Recently, we showed that platelet-derived growth factor-AA (PDGF-AA)/p70S6K signal transduction pathways in nonendothelial mesenchymal cells (NEMCs ; fibroblasts and vascular smooth muscle cells) was essential for therapeutic and tumor angiogenesis. The endogenous expression of VEGF is regulated and maintained by NEMCs and tumor cells via the autocrine system of the PDGF-AA/p70S6K pathways. The PDGF-AA/VEGF a … More xis, therefore, may be a ubiquitous autocrine system for enhancing angiogenic signals, and PDGF-AA, and its related pathways could be a more efficient target of angiogenic therapy for cancers than VEGF and its pathways.
On the other hand, transforming growth factor-beta (TGF-beta) is multifunctional polypeptides that regulate several functions, including cell growth and angiogenesis. The growth-inhibiting properties of TGF-beta have gained much attention into its role as a tumor suppressor. There is, however, now increasing evidence that TGF-beta switches roles, from tumor suppressor to tumor promoter, as the tumor progresses. Given the integral role of TGF-beta in the tumor progression, it follows that TGF-beta signaling offers an attractive target for cancer therapy. Interestingly, our recent independent study revealed that TGF-β inhibits VEGF expression upregulated by PDGF-AA/p70S6K pathways (unpublishied data), suggesting that TGF-beta may be a key regulator of angiogenic switch. Importantly, this hypothesis implies several possibilities as follows ; 1) TGF-beta is an attractive molecular marker for selective sensitivity to rapamycin, that is a specific inhibitor of p70S6K via reducing the activity of target of rapamycin ; 2) A combination therapy of anti-TGF-beta and anti-PDGF-AA/p70S6K signaling may be efficient target of antiangiogenic therapy for cancers. More understanding of pathophysiology and mechanism of angiogenic switch will allow us to develop clinically applicable strategies in the near future. Less

  • Research Products

    (5 results)

All 2010

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (1 results)

  • [Journal Article] Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2.2010

    • Author(s)
      Fujii T, et al.
    • Journal Title

      In Vitro Cell Dev Biol Anim. 46

      Pages: 487-491

    • Peer Reviewed
  • [Journal Article] An autocrine linkage between matrix metalloproteinase-14 and Tie-2 via ectodomain shedding modulates angiopoietin-1-dependent function in endothelial cells.2010

    • Author(s)
      Onimaru M, Yonemitsu Y, Suzuki H, Fujii T, Sueishi K.
    • Journal Title

      Arterioscler Thromb Vase Biol. 30

      Pages: 818-826

    • Peer Reviewed
  • [Journal Article] Implication of Extracapsular Invasion of Sentinel Lymph Nodes in Breast Cancer : Prediction of Nonsentinel Lymph Node Metastasis.2010

    • Author(s)
      Fujii T, et al.
    • Journal Title

      World J Surg. 34

      Pages: 544-548

    • Peer Reviewed
  • [Journal Article] Thickness of subcutaneous fat as a strong risk factor for wound infections in elective colorectal surgery : impact of prediction using preoperative CT.2010

    • Author(s)
      Fujii T, et al.
    • Journal Title

      Dig Surg. 27

      Pages: 331-335

    • Peer Reviewed
  • [Presentation] MCF-7に対するRapamycinのVEGF発現抑制による直接的抗腫瘍効果2010

    • Author(s)
      藤井孝明
    • Organizer
      第18回日本乳癌学会学術総会
    • Place of Presentation
      北海道・札幌市
    • Year and Date
      2010-06-24

URL: 

Published: 2012-02-13   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi