Alterations of tumor microenvironment during antiangiogenic therapy in colorectal cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390312
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KONNO Hiroyuki 浜松医科大学, 医学部, 教授 (00138033)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Kinji 浜松医科大学, 医学部附属病院, 講師 (20324361) ; OHTA Manabu 浜松医科大学, 医学部附属病院, 講師 (40397394) ; KIKUCHI Hirotoshi 浜松医科大学, 医学部, 助教 (70397389) ; MIYAZAKI Shinichiro 浜松医科大学, 医学部附属病院, 医員 (30571575)
• Co-Investigator(Renkei-kenkyūsha): BABA Satoshi 浜松医科大学, 医学部附属病院, 准教授 (10242760)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 抗血管新生治療 / 大腸癌 / 腫瘍微小環境 / 低酸素 / 癌悪性化 / 治療抵抗性

Outline of Final Research Achievements

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A has been used for colorectal cancer treatment. However, a number of preclinical reports indicate the development of resistance to anti-angiogenic therapy. In this study, we addressed the effects of anti-VEGF antibodies on the growth and malignant behavior of colorectal cancer cells using an orthotopic implantation model of TK-4, a solid tumor strain derived from a colon cancer patient, into nude mice. Intratumoral hypoxia induced by anti-VEGF antibody treatment resulted in induction of stanniocalcin 2 (STC2), a target gene of hypoxia inducible factor-1 (HIF-1), to enhance colon cancer cell growth and migration. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti-VEGF antibodies and rebound phenomenon after withdrawal of bevacizumab.

Free Research Field

消化器外科学