Investigation of mechanical properties of tumor microenvironment with spatial and temporal heterogeneity of oxygen tension for control of tumor cell behavior(Fostering Joint International Research)

2019 Fiscal Year Final Research Report

• Project/Area Number: 16KK0138
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Tohoku University
• Principal Investigator: Funamoto Kenichi 東北大学, 流体科学研究所, 准教授 (70451630)
• Project Period (FY): 2017 – 2019
• Keywords: マイクロ・ナノデバイス / 細胞・組織 / 生物・生体工学 / 流体工学 / ナノバイオ / マイクロ流体デバイス / がん微小環境 / 低酸素

Outline of Final Research Achievements

Effects of spatiotemporal heterogeneity of oxygen concentration on mechanical properties of cancer cells and the surrounding extracellular matrix were investigated. A 3-in-1 chip which reproduces in vivo microenvironment was developed and employed to simultaneously control oxygen tension and mechanical and chemical stimuli to cells. Proliferation and migration speed of human breast cancer cell (MDA-MB-231 cell line) were increased under hypoxia than those under normoxia. However, these tendencies became unclear when the cancer cells were co-cultured with the vascular endothelial cells. Contraction and degradation of collagen gel was promoted under the co-culture condition, but its speed was slowed down by hypoxic exposure. Thus, it was found that changes of the cancer cell behaviors and the surrounding extracellular matrix as well as their interactions were oxygen-dependent.

Free Research Field

生体工学、流体工学

Academic Significance and Societal Importance of the Research Achievements

がん微小環境では、細胞群の過剰な増殖により慢性的かつ不均一な低酸素状態が生成されるとともに、未成熟な血管網の形成に起因して一過性の低酸素負荷と再酸素化が生じる。本研究では、酸素濃度の変化が、がん細胞やその周囲の細胞外マトリクスの力学的特性と、それらの間の相互作用に与える影響の一端を解明した。本研究で観察された酸素濃度に依存する微小環境における現象は、がんの増殖と転移の問題に限らず、様々な疾患の予防や治療、再生医療の進展に重要な知見をもたらすものである。