Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer

BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

PerinataI compilcations and marker of infection: macrophage colony stimulating factor

Macrophage colony stimulating factor [M-CSF] is a hematopoietic growth factor produced by monocytes, granulocytes, endothelial cells, and fibroblasts. M-CSF augments the ability of mature macrophages and monocytes to kill microorganisms by enhancing their production of superoxides and cytokines. This study was designed to determine whether perinatal complications induce the production of M-CSF or sepsis, so we have compared M-CSF levels in the cord blood between group I normal neonates, group lla neonates with perinatal complications e.g., premature rupture of membranes [PROM], C.S., prematurity, post data, diabetic and hypertensive mothers and group lib neonates with complications after getting infected. As regard the results of MCSF among the studied groups it was found that M-CSF level was higher in group ha and group IIb than group I [2827.3 +/- 1391.3 pg/mi], [3840.3 +/- 806.9 pg/mI], [657.5 +/- 458,3 pg/mI] respectively, and this differences were highly statistically significant. it was found also non significant difference between M-CSF levels among the diverse perinatal complications what so ever, The level of M-CSF in group lib [who developed infection] was higher after developing sepsis [3993.9 +/- 983. 2pg/ml] than before [3840.3 +/- 806.9 pg/mI] but without significant statistical difference. M-CSF levels in the cord blood from neonates with perinatal complications were significantly higher than those in the cord blood sampled from normal neonates and determination of its level in the neonates with perinatal complication will not be of vulnerable clinical significance as an early marker of sepsis

Assessment of the role of M-CSF in expansion of CD 14 + CD 16 + blood monocytes in patients undergoing haemodialysis

The immunodeficiency of patients with chronic renal failure [CRF] is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is a key factor in these immunological disorders. A normal subpopulation of blood monocytes coexpressing CD 16 antigen and low level of CD 14 antigen [CD 14+ CD16+] has recently been identified. In this study, we measured the plasma levels of some relevant haemopoietic growth factors and cytokines in 32 patients suffering from CRF who were undergoing haemodialysis and 12 healthy controls, using an ELISA technique. The plasma levels of macrophage - colony stimulating factor [M- CSF] were significantly increased in patients compared to controls [p < 0.001], while the increase in granulocyte macrophage colony stimulating factor [GM - CSF] and interleukin 10 [IL - 10] was insignificant [p > 0.05]. We also examined the immunophenotype of blood monocytes in haemodialysed patients using two - colour immunofluorescence flow cytometry. A significant increase in the percentage and absolute number of CD 14+ CD 16+ monocytes was noted in patients compared to controls [p<0.00l]. On the other hand, the percentage of CD 14++ CD 16- regular monocytes was slightly but significantly decreased [p < 0.01], although their absolute number did not differ significantly [p > 0.05]. Significant correlation was detected between plasma levels of M - CSF and the number of CD 14+ CD 16+ monocytes.Our results suggest that increased endogenous levels of M-CSF plays a major role in the chronic activation of monocyte subpopulations and may be responsible for the expansion of CD 14+ CD 16+ blood monocytes which leads to multiple metabolic, haematologic and immunologic defects in CRF patients under haemodialysis

Inverse correlation between macrophage-colony stimulating factor, cholesterol and high density lipoprotein cholesterol in Kawasaki disease.

Kawasaki disease (KD) is a childhood-onset vascular disease. We assessed the concentrations of macrophage-colony stimulating factor (M-CSF) and those of lipids in sera from patients with KD. The M-CSF concentration in patients with acute-phase KD was 2,914+/-159 U/ml, significantly higher than that in control subjects with Infectious diseases (1,241+/-96 U/ml). The elevated levels of this cytokine in the acute phase fell to 1,319+/-138 U/ml in the convalescent phase. Total and high-density lipoprotein cholesterol concentrations in acute phase KD (113.8+/-8.4 and 21.5+/-2.3 mg/dl, respectively) were lower than in the infectious disease controls (195.8+/-7.0 and 62.5+/-1.8 mg/dl). The elevation of M-CSF correlated with the decrease of total and high-density lipoprotein cholesterol. Overproduction of macrophage-colony stimulating factor activates macrophages and monocytes and may disturb the lipid metabolism. Both effects could contribute to vasculitis in KD.