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Updated: Dec 25, 2025
Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
The EGFL7-ITGB3-KLF2 axis enhances survival of multiple myeloma in preclinical models
Yousef Salama1,2, Andries Hendrik Heida1, Kazuaki Yokoyama3
1Division of Stem Cell Dynamics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract:
Angiogenic factors play a key role in multiple myeloma (MM) growth, relapse, and drug resistance. Here we show that malignant plasma cells (cell lines and patient-derived MM cells) express angiocrine factor EGF like-7 (EGFL7) mRNA and protein. MM cells both produced EGFL7 and expressed the functional EGFL7 receptor integrin β 3 (ITGB3), resulting in ITGB3 phosphorylation and focal adhesion kinase activation. Overexpression of ITGB3 or EGFL7 enhanced MM cell adhesion and proliferation. Intriguingly, ITGB3 overexpression upregulated the transcription factor Krüppel-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. EGFL7 expression was found in certain plasma cells of patients with refractory MM and of patients at primary diagnosis. NOD.CB17-Prkdc
Insights
Multiple myeloma cells produce EGFL7, a factor that promotes their growth and survival. Targeting this EGFL7-ITGB3-KLF2 loop, alongside bortezomib, offers a new strategy against this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Angiogenic factors are crucial in multiple myeloma (MM) progression, drug resistance, and relapse.
- Understanding novel molecular pathways driving MM is essential for developing effective therapies.
Purpose of the Study:
- To investigate the role of the angiocrine factor EGFL7 in multiple myeloma (MM) pathogenesis.
- To elucidate the molecular mechanisms by which EGFL7 influences MM cell survival and proliferation.
Main Methods:
- Analysis of EGFL7 and ITGB3 expression in MM cell lines and patient samples.
- Investigating the EGFL7-ITGB3-KLF2 signaling loop using molecular assays.
- In vitro and in vivo studies using EGFL7 knockdown and neutralizing antibodies.
- Assessment of bortezomib's effect on EGFL7, ITGB3, and KLF2 expression.
Main Results:
- Malignant plasma cells express EGFL7 and its receptor ITGB3, activating signaling pathways.
- An amplification loop involving EGFL7, ITGB3, and KLF2 promotes MM cell adhesion, survival, and proliferation.
- EGFL7 expression is detected in refractory MM patients and correlates with disease.
- EGFL7 inhibition reduces MM growth in vitro and in vivo.
- Bortezomib upregulates EGFL7, ITGB3, and KLF2 in MM cells.
Conclusions:
- The EGFL7-ITGB3-KLF2 axis is a critical survival pathway in multiple myeloma.
- Targeting EGFL7 signaling, potentially in combination with bortezomib, represents a promising therapeutic strategy for MM.
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