2021 Fiscal Year Research-status Report
The mechanism of resistance to cancer uncovered by Sipa1 deficiency
| Project/Area Number |
21K15466
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| Research Institution | Kyoto University |
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Principal Investigator |
徐 彦 京都大学, 医学研究科, 特定助教 (00896631)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | mesenchymal stroma cells / Sipa1 / T cell infiltration |
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| Outline of Annual Research Achievements |
1. Three distinct subsets of tumor mesenchymal stroma cells (MSCs) were identified. They had different functions in tumor tissues and their comparable phenotypes could be barely detectable in normal tissues. In the tumor tissues of Sipa1 deficient host, the proliferation and differentiation of reticular fibroblastic like tumor MSCs (FB/FC subtype) were activated, but myofibrobrastic like MSCs (FA subtype) were not be affected.
2. Tumor tissues of Sipa1 deficient host showed a remarkably elevated expression of selected T cell-chemokines in association with a significant increase in T cell infiltration. Tumor MSCs of Sipa1 deficient host also showed an increased expression of selected chemokine genes. qPCR analysis confirmed that the tumor-associated MSCs of Sipa1 deficient host show a markedly increased expression of T cell-chemokine genes (Cxcl9, 10), and this was associated with the increased T cell infiltration in tumor tissues. Immunostaining analysis also reveals strong expression of Cxcl9 in the reticular MSCs surrounding tumor cells of KO hosts, which was associated with a significant accumulation of T cells.
3. In Sipa1 deficient tumor MSCs IFN gama-signaling pathway was enhanced. It may underlie the remarkably augmented T-cell chemokine gene expression in Sipa1 deficient MSCs in tumor tissues.
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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
Identified the tumor MSCs subtypes by FACS and immunostaining analysis as planed, and performed the gene expression analysis in MSCs. Clarified MSCs in tumor tissues of Sipa1 deficient host showed a remarkably elevated expression of selected T cell-chemokines in association with a marked increase in T cell infiltration.
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| Strategy for Future Research Activity |
Clarify factors and signal pathways inducing such functional diversification of tumor MSCs in the anti-tumor mechanism. Advanced gene and protein expression analysis of MSC subtypes will be performed to clarify their anti tumor affection, especially the local T cell response-inducing effect.
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| Causes of Carryover |
(Reasons)
Some kinds of antibodies and materials for the experiment were difficult to purchase because of the Covid-19, so I could not perform the planned experiments.
(Usage Plan)
Experiments will be performed next fiscal year as soon as the antibodies and materials are delivered.
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