The role of cancer metastasis in tumor vascular endothelial cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Itoh Fumiko 東京薬科大学, 生命科学部, 准教授 (70502582)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: TGFβ / 血管新生 / がん転移 / 遺伝子改変マウス / CreER

Outline of Final Research Achievements

At the late stage of tumorigenesis, cancer cells produce TGF-β which promotes tumor proliferation and metastasis. Although angiogenesis is important for the growth of cancer cells, it remains veiled how abundant TGF-β plays a role in tumor angiogenesis. Hence, we have generated tamoxifen-inducible knockout mice of TGF-β type II receptor； TβRIIfl/fl; Pdgfb-iCreER (TβRIIiECΔ). When Lewis lung carcinoma (LLC) cells were transplanted into　TβRIIiECΔ mice, there was no difference in tumor weight compared to control mice. Tumors formed in TβRIIiECΔ mice had increased angiogenesis, but the blood vessels were fragile and leaky. As blood flow was not secured in tunors, hypoxia could be observed in the tumors from TβRIIiECΔ mouse. When cancer cells invading blood vessels were counted using FACS, we found that circulating tumor cells were increased in TβRIIiECΔ mice. These results suggest that the TGF-β signal in endothelial cells inhibits angiogenesis and metastasis.

Free Research Field

腫瘍