肺腺癌の転移成立を防ぐための研究

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: 地方独立行政法人神奈川県立病院機構 (2011); Kanagawa Cancer Center Research Institute (2010)
• Principal Investigator: SAKUMA Yuji 地方独立行政法人神奈川県立病院機構, 神奈川県立がんセンター(臨床研究所)・がん分子病態学部, 副技幹 (10364514)
• Project Period (FY): 2010 – 2011
• Keywords: 肺腺癌 / 転移 / アポトーシス / EGFR / Src

Research Abstract

EGFR-mutant lung adenocarcinoma cells in suspension culture system undergo massive apoptosis by treatment with EGFR tyrosine kinase inhibitors(TKIs). On the other hand, EGFR-mutant cells in monolayer culture system are much more resistant to EGFR TIKs-induced apoptosis than suspended tumor cells, although the phosphorylation of EGFR expressed in EGFR-mutant cells is completely suppressed in either culture condition. Also intrasinus floating tumor cells in metastasis-positive lymph nodes from EGFR-mutant lung adenocarcinoma patients expressed mutant specific EGFR in the same way as extracellular matrix adhesive tumor cells. These findings suggest that the tumor cells floating in vessels would be highly susceptible to EGFR TKIs.

Research Products

• [Journal Article] WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors (2012)
  • Author(s): Sakuma Y, Yamazaki Y, Nakamura Y, Yoshihara M, Matsukuma S, Nakayama H, Yokose T, Kameda Y, Koizume S, Miyagi Y.
  • Journal Title: Lab Invest Volume: 92 Pages: 371-383
  • Peer Reviewed
• [Journal Article] ABT-263, a Bcl-2 inhibitor, enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis (2011)
  • Author(s): Sakuma Y, vTsunezumi J, Nakamura Y, Yoshihara M, Matsukuma S, Koizume S, Miyagi Y.
  • Journal Title: Oncol Rep Volume: 25 Pages: 661-667
  • Peer Reviewed
• [Presentation] EGFR-mutant lung adenocarcinoma cells depend critically on EGFR activation to thrive in anchorage-independent conditions (2011)
  • Author(s): Sakuma Y, Nakamura Y, Yoshihara M, Koizume S, Miyagi Y
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2011-10-05
• [Presentation] 肺腺癌におけるanoikis抵抗性の研究 (2011)
  • Author(s): 佐久間裕司、中村圭靖、横瀬智之、亀田陽一、宮城洋平
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2011-04-28
• [Presentation] ABT-263 enhances the susceptibility of lung adenocarcinoma cells treated with Src inhibitors to anoikis (2010)
  • Author(s): Sakuma Y, Nakamura Y, Yoshihara M, Koizume S, Miyagi Y.
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2010-09-22
• [Remarks]
  • URL: http://kcch.kanagawa-pho.jp/kccri/project/lungcancer.html