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Updated: Oct 12, 2025
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Increased Plasma GDF15 Is Associated with Altered Levels of Soluble VEGF Receptors 1 and 2 in Symptomatic Multiple
Josefin Hidman1,2, Anders Larsson1,3, Måns Thulin4
1Department of Medical Science, Uppsala University, Uppsala, Sweden.
Introduction:
In multiple myeloma, there is an increase in bone marrow microvascular density and enhanced renal lymphangiogenesis. Increased levels of the proangiogenic protein growth differentiation factor-15 (GDF15) have previously been reported to be associated with poor prognosis in myeloma. A possible association between GDF15 and the soluble forms of vascular endothelial growth factor receptors (sVEGFR) 1 and 2 has not yet been investigated, and a role for these receptors in pathological angiogenesis in myeloma is still to be defined.
Methods:
Plasma levels of GDF15 and sVEGFR1 and 2 were determined by ELISA in patients with smouldering multiple myeloma (sMM), patients with symptomatic multiple myeloma (abbreviated as MM), and healthy controls. The levels were compared between the three groups, and correlation coefficients were calculated, as were Kaplan-Meier curves for GDF15 and sVEGFR1 and sVEGFR2.
Results:
Levels of GDF15 were significantly higher in MM than in both patients with sMM and controls. A gradual decrease in mean sVEGFR1 concentration was observed, with MM > sMM > controls. Mean sVEGFR2 was lower in patients with MM than in controls. There was a positive correlation between GDF15 and sVEGFR1, and GDF15 correlated negatively with sVEGFR2. High GDF15 (>3 ng/mL) was associated with poor prognosis.
Conclusion:
In multiple myeloma, increased expression of GDF15 correlates positively with sVEGFR1 and negatively with sVEGFR2. It is possible that the altered levels of sVEGFR1 and 2 contribute to the increased angio- and lymphangiogenesis observed in myeloma.
Insights
Growth Differentiation Factor-15 (GDF15) levels are higher in multiple myeloma (MM) patients and correlate with poor prognosis. GDF15 shows a positive association with soluble vascular endothelial growth factor receptor 1 (sVEGFR1) and a negative association with sVEGFR2 in MM.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Multiple myeloma (MM) is characterized by increased bone marrow vascularity and lymphangiogenesis.
- Elevated Growth Differentiation Factor-15 (GDF15) is linked to poor prognosis in MM.
- The relationship between GDF15 and soluble vascular endothelial growth factor receptors (sVEGFR1, sVEGFR2) in MM remains undefined.
Purpose of the Study:
- To investigate the association between GDF15, sVEGFR1, and sVEGFR2 in patients with multiple myeloma.
- To determine the role of these factors in the angiogenesis and lymphangiogenesis observed in MM.
Main Methods:
- Plasma levels of GDF15, sVEGFR1, and sVEGFR2 were measured using ELISA in patients with symptomatic MM, smoldering MM (sMM), and healthy controls.
- Statistical analyses included comparisons between groups and correlation analyses (Pearson correlation coefficients).
- Kaplan-Meier curves were used to assess the prognostic value of GDF15, sVEGFR1, and sVEGFR2.
Main Results:
- GDF15 levels were significantly elevated in MM patients compared to sMM patients and controls.
- sVEGFR1 concentrations decreased progressively from MM to sMM to controls, while sVEGFR2 levels were lower in MM patients than in controls.
- A positive correlation was found between GDF15 and sVEGFR1, and a negative correlation between GDF15 and sVEGFR2. High GDF15 levels (>3 ng/mL) were associated with poor prognosis.
Conclusions:
- Increased GDF15 expression in MM correlates positively with sVEGFR1 and negatively with sVEGFR2.
- Altered levels of sVEGFR1 and sVEGFR2 may contribute to the enhanced angio- and lymphangiogenesis in multiple myeloma.
