- Laboratory of Cell Dynamics
- Research Theme
- Collective Behavior and 3D Morphogenesis of Epithelial Cells, Cancer Cell Invasion
- Research Keywords
collective cell movement, 3D morphogenesis, cancer cell invasion
Overview of Research
■3D morphogenesis of epithelial sheets using viscoelastic substrates
3D morphogenesis is an essential process for various phenomena such as embryonic development and tissue formation. Mechanical properties of the extracellular matrix are understood as factors that affect the cell behavior. We show that a collagen gel overlay induced epithelial sheet folding from the periphery that migrated inwardly, resulting in the formation of a 3D luminal structure in a collagen gel. We also cultured epithelial cells on a viscous substrate. The cells presented a tulip hat-like 3D morphology induced by the deformation of the peripheral substrate.
■Acceleration of metastatic growth of cancer cells induced by substrate stiffness
Recent studies have shown that stiff substrates trigger cancer progression such as metastasis and cell proliferation. For example, it is well known that malignant breast tissues are stiff compared with normal mammary tissues. We found that stiff substrates enhanced cancer progression by upregulating matrix metalloproteinase-7 expression, which is an indicator of poor prognosis, through the positive feedback loop of yes-associated protein, epidermal growth factor receptor, integrin and myosin regulatory light chain in colorectal cancer.
- School of Science:
Biological Science course (Macromolecular Functions), Core Laboratories
- Graduate School of Life Science:
Division of Soft Matter, Soft Matter Biophysics
S. Ishida-Ishihara, M. Akiyama, K. Furusawa, I. Naguro, H. Ryuno, T. Sushida, S. Ishihara, and H. Haga: Osmotic Gradients Induce Stable Dome Morphogenesis on Extracellular Matrix, Journal of Cell Science, 133, jcs243865 (2020).
Y. Kumagai, J. Nio-Kobayashi, S. Ishida-Ishihara, H. Tachibana, R. Omori, A. Enomoto, S. Ishihara, and H. Haga: The intercellular expression of type-XVII collagen, laminin-332, and integrin-β1 promote contact following during the collective invasion of a cancer cell population, Biochem. Biophys. Res. Commun., 514, 1115-1121 (2019).
S. Ishihara, K. Aoki, T. Mizutani, M. Amano, S. Nishimura, and H. Haga: Glycosphingolipid GM2 Induces Invasiveness in Irradiation-tolerant Lung Cancer Cells, Cell Structure and Function, 43, 177-185 (2018).
Koh, K. Furusawa, and H. Haga: Anisotropic Multi-channel Collagen Gel (MCCG) Guides the Growth Direction of the Neurite-like Processes of PC12 Cells, Scientific Reports, 8, 13901, 1-10 (2018).
Oyama, K. Takahashi, Y. Tanaka, H. Takemoto, and H. Haga: Long-term Culture of Human iPS Cell-derived Telencephalic Neuron Aggregates on Collagen Gel, Cell Structure and Function, 43, 85-94 (2018).
Akiyama, T. Sushida, S. Ishida, and H. Haga: Conformational Mathematical Model of Collective Cell Migrations Based on Cell Polarity, Dev. Growth Differ., 59, 471-490 (2017).
Nukuda, H. Endoh, M. Yasuda, T. Mizutani, K. Kawabata, and H. Haga: Role of ATF5 in the Invasive Potential of Diverse Human Cancer Cell Lines, Biochem. Biophys. Res. Commun., 474, 509–514 (2016).
Refer to HOKKAIDO UNIVERSITY RESEARCHERS DIRECTORY
– Time: Anytime during the lecture period
– Place: Science Bldg. No.2, 6F, #2-612
Please contact in advance by E-mail.
- Faculty of Advanced Life Science, Department of Advanced Transdisciplinary Sciences, Cellular Dynamics Science
- Frontier Research Center for Advanced Material and Life Science, Global Collaboration Unit, Soft Matter Collaborative Research Unit