2020 Fiscal Year Final Research Report
Studies for the COX-HDAC6 axis in extra-mammary Paget disease
| Project/Area Number |
19K17812
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | HDAC6 / 乳房外Paget病 / COX2 / 浸潤 / 転移 |
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| Outline of Final Research Achievements |
For the effective treatment in advanced extramammary Paget disease, we analyzed HDAC6-COX2-related molecules and studied their role in invasion and metastasis. Activation of HDAC6-COX2-PGE2 was examined in co-culture systems as well as by immunostaining in human tumors.
HDAC6-COX2 may play an important role in the microenvironment formed by tumor cells and surrounding cancer-related fibroblasts (CAFs). Immunostaining revealed that HDAC6 was overexpressed in extramammary Paget's disease in the advanced stage, and many fibroblasts that appeared to be αSMA-positive CAF were found around it. These HDAC6-positive cells formed agglomerates and showed the dynamics of collective cell invasion. It was suggested that the secretion of PGE in extramammary Paget's disease is involved in the induction of overexpression of HDAC6 and may be involved in the acquisition of infiltration / metastatic ability.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
進行期の乳房外Paget病に対して有効な化学療法は無く、新たな治療薬の開発が切望されている。炎症性の症状を思わせる、乳房外Paget病の患者は、比較的多く、自分の研究テーマであるHDAC6とCOX2が極めて近い位置関係で作用している事が明らかになった。既にCOX2阻害薬は臨床応用されちぇおり、HDAC6阻害薬も臨床試験に入っている。本研究の基礎データは、今後の乳房外Paget病の治療に対して重要な意義を持つと思われる。
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