2019 Fiscal Year Annual Research Report
三次元膵癌モデルを用いた細胞と間質の相互作用および腫瘍の可塑性の解析
| Project/Area Number |
18J20132
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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| Research Fellow |
Hoh Hong Huat 沖縄科学技術大学院大学, 科学技術研究科, 特別研究員(DC1)
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| Project Period (FY) |
2018-04-25 – 2021-03-31
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| Keywords | pancreatic cancer / tumor microenvironment |
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| Outline of Annual Research Achievements |
In this fiscal year, I was tasked to explore the potential of a designed self-assembling integrin-targeting peptides in altering pancreatic cancer phenotype. The self-assembling peptides were characterized by transmission electron microscopy (TEM) and ultraviolet spectroscopy. After treatment with human pancreatic cancer cells, scanning electron microscopy (SEM) imaging showed that the peptides self-assembled into a nanofiber meshwork on the cell surface with an increasing density when longer incubation time was done. In vitro functional assays, including MTT cell viability assay, wound healing assay and invasion assay were carried out. Results showed that the treated cells were largely viable but migration and invasion were severely impaired after treatment with the peptides. In order to investigate the molecular mechanism behind this inhibition, RNA sequencing was conducted. Transcriptomic analysis demonstrated that cells underwent significant gene expression changes, especially after treatment for 12 and 36h. Genes that are involved in ATP-dependent cellular processes were significantly downregulated, hinting that the binding of self-assembling peptides impacted access to macromolecules for energy-demanding processes. Comprehensive metabolic assays showed an initial increase of glycolysis at 6h and 12h but, followed by a sharp decrease after 24h and 36h. These findings indicated that cellular metabolism was altered by the peptides in their microenvironment and subsequently, impacting the cellular processes and biological functions.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The plan went as it was expected. All the in vitro and molecular studies were conducted and results were analyzed and summarized within the fiscal year.
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| Strategy for Future Research Activity |
In the next fiscal year, I will continue to verify the molecular effects of the self-assembling peptide designed to target pancreatic tumor microenvironment using in vivo animal xenotransplantation system. Human pancreatic cancer cells are harvested and xenografted into nude mice to generate tumors. Tumors generated are then subjected to peritumoral injections of the investigational peptides every three days for up to a maximum of five doses. In vivo animal imaging will be used to access the tumor growth as well as to estimate the tumor size. After sufficient effect on tumor growth is achieved, the tumors are dissected from the mice to be accessed for their size, volume and histology in order to study the effect of targeting the tumor stroma. The results will be combined with previous in vitro findings to summarize the potential effect of targeting the tumor microenvironment of pancreatic cancer using investigational biological agent.
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Research Products
(2 results)
