Inflammatory response and tumor growth in lung cancer stroma

• Project/Area Number: 18591569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kurume University
• Principal Investigator: TAKAMORI Shinzo Kurume University, School of medicine, Surgery, Associate Professor (50197208)
• Co-Investigator(Kenkyū-buntansha): TERAZAKI Yasuhiro Kurume University, School of medicine, Surgery, Assistant Professor (30279187) ; KIMURA Yusuke Kurume University, School of medicine, Surgery, Assistant Professor (90360297)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: Lung cancer / Macrophage / Angiogenesis / Cancer stroma / 癌間

Research Abstract

The focus of the present study was whether and how infiltrating macrophages play a role in angiogenesis and the growth of cancer cells in response to the inflammatory cytokine interleukin (IL)-1beta. Lewis lung carcinoma cells overexpressing IL-1beta grew faster and induced greater neovascularization than a low IL-1beta-expressing counterpart in vivo. When macrophages were depleted using clodronate liposomes, both neovascularization and tumor growth were reduced in the IL-1beta-expressing tumors. Co-cultivation of IL-1beta-expressing cancer cells with macrophages synergistically augmented neovascularization and the migration of vascular endothelial cells. In these co-cultures, production of the angiogenic factors vascular endothelial growth factor-A and IL-8, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 were increased markedly. The production of these factors, induced by IL-1beta-stimulated lung cancer cells, was blocked by a nuclear factor (NF)-kappaB inhibitor, and also by the knockdown of p65 (NF-kappaB) and c-Jun using small interference RNA, suggesting involvement of the transcription factors NF-kappaB and AP-1. These results demonstrated that macrophages recruited into tumors by monocyte chemoattractant protein-1 and other chemokines could play a critical role in promoting tumor growth and angiogenesis, through interactions with cancer cells mediated by inflammatory stimuli.

Research Products

• [Journal Article] Inflammatory Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis (2007)
  • Author(s): Kimura YN, Watari K, Fotovati A, Hosoi F, Yasumoto K, Izumi H, Kohno K, Umezawa K, Iguchi H, Shirouzu K, Takamori S, Kuwano M, Ono M
  • Journal Title: Cancer Science 98 Pages: 2009-2018
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inflammatorylnflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis. (2007)
  • Author(s): Kimura YN, Watari K, Fotovati A, Hosoi F, Yasumoto K, Izumi H, Kohno K, Umezawa K, Iguchi H, Shirouzu K, Takamori S, Kuwano M, Ono M
  • Journal Title: Cancer Science 98 Pages: 2009-2018
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] InflammatoryInflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis (2007)
  • Author(s): Kimura YN, Watari K, Fotovati A, Hosoi F, Yasumoto K, Izumi H, Kohno K, UmezawaI K, Iguchi H, Shirouzu K, Takamori S, Kuwano M, Ono M
  • Journal Title: Cancer Science 98 Pages: 2009-2018
  • Peer Reviewed
• [Presentation] The role of macrophages in tumor growth and angiogenesis by lung cancer cells-inhibition by bisphosphonate-liposomes (2006)
  • Author(s): Kimura YN, Nakao S, Basaki Y, Ueda S, Takamori S, Shirouzu K, Kuwano M, Ono M
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC,USA
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The role of macrophages in tumor growth and angiogenesis by lung cancer cells-inhibition by bisphosphonate-liposomes. (2006)
  • Author(s): Kimura YN, Nakao S, BasakiY, Ueda S, Takamori S, Shirouzu K, Kuwano M, Ono M
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
  • Description: 「研究成果報告書概要(欧文)」より