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Published on: July 17, 2016
Platelet factor-4 and its p17-70 peptide inhibit myeloma proliferation and angiogenesis in vivo
Longjiang Yang1, Juan Du, Jian Hou
1Department of Hematology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Rd, Shanghai 200003, China.
Background:
Angiogenesis plays an important role in the development of multiple myeloma (MM). The interaction between MM cells and the bone marrow microenvironment stimulates the proliferation and migration of endothelial progenitor cells (EPCs). Vascular endothelial growth factor (VEGF) contributes to the formation of new blood vessels by actively recruiting circulating EPCs. The production of proangiogenic and antiangiogenic factors is also dysregulated in MM. Platelet factor 4 (PF4) is a potent angiostatic cytokine that inhibits angiogenesis and tumor growth in several animal models.
Methods:
In this study, we stably transfected human myeloma cell lines with the PF4 gene or the sequence encoding its more potent p17-70 peptide and investigated the effects of PF4 and p17-70 on angiogenesis and tumor growth in vitro and in a SCID-rab myeloma model.
Results:
PF4 and p17-70 significantly attenuated VEGF production, both in vitro and in vivo. In a migration study using a Transwell system, PF4 or p17-70 markedly suppressed the migration of co-cultured human endothelial progenitor cells. PF4 or p17-70 also caused a significant reduction in microvessel densities in myeloma xenografts and markedly reduced the tumor volume in the SCID mice. Kaplan-Meier analysis demonstrated that PF4 and p17-70 significantly extended the overall survival of SCID mice bearing human myeloma xenografts.
Conclusions:
Our findings indicate that PF4 or p17-70 could be valuable in combating multiple myeloma by disrupting tumor angiogenesis.
Insights
Platelet factor 4 (PF4) and its peptide p17-70 inhibit multiple myeloma (MM) growth by blocking blood vessel formation. These findings suggest PF4 and p17-70 as potential therapies for MM by targeting tumor angiogenesis.
Area of Science:
- Oncology
- Vascular Biology
- Molecular Medicine
Background:
- Angiogenesis is crucial for multiple myeloma (MM) development, driven by endothelial progenitor cell (EPC) proliferation and migration.
- Vascular endothelial growth factor (VEGF) promotes new blood vessel formation in MM by recruiting EPCs.
- Platelet factor 4 (PF4) is an anti-angiogenic factor that inhibits tumor growth.
Purpose of the Study:
- To investigate the effects of PF4 and its potent peptide p17-70 on angiogenesis and tumor growth in multiple myeloma.
- To evaluate the therapeutic potential of PF4 and p17-70 in preclinical models of MM.
Main Methods:
- Human myeloma cell lines were stably transfected with PF4 or the p17-70 peptide sequence.
- In vitro and in vivo studies were conducted using a SCID-rab myeloma model.
- Effects on VEGF production, EPC migration, microvessel density, and tumor volume were assessed.
Main Results:
- PF4 and p17-70 significantly reduced VEGF production in vitro and in vivo.
- PF4 and p17-70 suppressed endothelial progenitor cell migration.
- PF4 and p17-70 decreased microvessel density, tumor volume, and extended survival in SCID mice xenografts.
Conclusions:
- PF4 and p17-70 demonstrate potent anti-angiogenic and anti-tumor effects in multiple myeloma models.
- PF4 and p17-70 hold promise as novel therapeutic agents for combating multiple myeloma by disrupting tumor angiogenesis.
