2019 Fiscal Year Research-status Report
Role of the angiocrine factor Egfl7 in multiple myeloma progression and drug resistance
| Project/Area Number |
19K08857
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| Research Institution | Juntendo University |
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Principal Investigator |
ハイジッヒ ベアーテ 順天堂大学, 医学(系)研究科(研究院), 特任准教授 (30372931)
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| Co-Investigator(Kenkyū-buntansha) |
服部 浩一 順天堂大学, 医学(系)研究科(研究院), 特任先任准教授 (10360116)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | multiple myeloma / cell growth / integrin / proliferation / KLF2 / ITGB3 / adhesion / proliferation |
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| Outline of Annual Research Achievements |
We showed Egfl7 and Beta3 integrin expression in patient samples and cell lines . Functionally, we showed that overexpression increased, while knockdown decreased myeloma cell proliferation.
We used 2 murine models of myeloma to show that inhibition of Egfl7 using neutralizing antibodies against Egfl7 prevented myeloma growth.
Mechanistically we demonstrated that overexpression of ITGB3 or EGFL7 enhanced MM cell adhesion and proliferation. Intriguingly, ITGB3 overexpression upregulated the transcription factor Krueppel-like factor 2 (KLF2), which further enhanced EGFL7 transcription in MM cells, thereby establishing an EGFL7-ITGB3-KLF2-EGFL7 amplification loop that supports MM cell survival and proliferation.
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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
no major problems experimentally (until the outbreak of the coronavirus pandemic).
Since March 2020 the research center and its facilities can not be used as frequently. We all hope research efforts around the world will help to prevent more pain and death.
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| Strategy for Future Research Activity |
We are currently examining how Egfl7 can modulate other cellular functions, and are screening for other cellular receptors that might be involved multiple myeloma pathology.
We also are testing drugs that blocks those other receptors as a novel treatment option for multiple myeloma
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