Identification of VEGF-independent angiogenic factors in non-small cell lung cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Eguchi Ryoji 兵庫医科大学, 医学部, 助教 (00461088)
• Co-Investigator(Kenkyū-buntansha): 若林 一郎 兵庫医科大学, 医学部, 教授 (70220829)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管新生 / 非小細胞肺癌 / 無血清培養 / 3次元培養 / VEGF / HDGF / FGF-2

Outline of Final Research Achievements

In the present study, I aimed at identification of angiogenic factors derived from non-small cell lung cancer (NSCLC). EBC-1, a NSCLC cell line, was incubated in serum-free culture, in which eleven candidates were found by mass spectrometry. Among the eleven proteins, vascular endothelial growth factor (VEGF) and hepatoma-derived growth factor (HDGF) regulated angiogenesis induced by EBC-1 cells. However, VEGF and HDGF were not involved in angiogenesis induced by another NSCLC cell line, Lu99. By gene microarray in EBC-1 and Lu99 cells, three candidates were expressed in only Lu99 cells. Among the three genes, fibroblast growth factor-2 (FGF-2) regulated angiogenesis induced by Lu99 cells. These results suggest that HDGF enhances VEGF-dependent angiogenesis and FGF-2 is a VEGF-independent angiogenic factor in human NSCLC cells.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

本邦で承認されている非小細胞肺癌の抗血管新生療法は、奏効率、無増悪生存期間、全生存期間の延長が報告されているが、それでもその平均生存期間は1年半と短いことから、他の血管新生因子の関与が考えられる。これまでにも非小細胞肺癌のVEGFとは異なる血管新生因子としてHDGFやFGF-2は報告されていたが、本研究の成果はそれらの報告を裏付ける研究結果となった。HDGFやFGF-2をターゲットとした抗血管新生療法の開発が期待される。