Abstract
Release of matrix metalloproteinase 9 (MMP-9), neutrophil elastase and cathespin-G from bone marrow stromal cells and granulocytic precursors in response to cytokines and chemotherapy results in degradation of important retention signals such as SDF-1 and V-CAM and promotes egress of progenitor cells from the bone marrow into the peripheral blood. In this study we investigated whether plasma MMP-9 levels could predict efficiency of haemopoietic progenitor cell mobilization
Methods: Plasma MMP-9 levels were assessed at 0, 24 and 48 hours in chemotherapy naïve patients with solid tumours. Patients were randomised to receive a single administration of 6, 12 or 18mg of pegfilgrastim on day 1 or daily administration of filgrastim 10 μg/kg/day from day 1 until day 7. Eight subjects were studied in each group. Each group was balanced in terms of baseline characteristics. Blood samples for peripheral CD34+ cell count and colony assays were collected on the first 7 days and day 9 and 12 post therapy.
Results: The most common tumour types were non-small cell lung cancer (n = 15; 47%) and ovarian cancer (n = 9; 28%). In the filgrastim and pegfilgrastim 6mg, 12mg and 18mg groups a significant rise in MMP-9 levels were seen between 0 and 24 hours (380 vs. 2020 ng/ml, p=0.002; 220 vs 1920 ng/ml, p=0.015; 610 vs. 2510 ng/ml, p=0.0002 and 250 vs. 2050 ng/ml, p=0.003, respectively). In all groups, there was no significant increase in plasma MMP-9 levels between 24 and 48 hours. No significant differences in MMP-9 levels were observed between the 4 cytokine groups over 0 to 48 hours. Across all the groups no significant correlation was seen between plasma MMP-9 levels and peak colony forming units (CFU) per millilitre of blood and peak CD34 positive cells per millilitre of blood (r2=0.103, p=0.08; r2=0.09, p=0.1, respectively).
Conclusion: In all cytokine groups, a significant increase in plasma MMP-9 levels occurred between day 1 and 2. No association between MMP-9, levels numbers of peripheral blood CD34 positive cells and CFU levels could be established. Plasma MMP-9 levels were not affected by pegfilgrastim dose. MMP-9 does not appear to be a predictor of mobilization efficiency for filgrastim or pegfilgrastim at doses up to 18mg.
Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts