(iv) Systemic therapies targeting CSF1
receptor show promising results as novel treatment method for diffuse-TGCT.
Moreover we observed a clear increase in the expression of IL1[beta] in NP samples, but no change in the expression of TNF, and a minor increase in the expression of macrophage colony stimulating factor Csf1 180 minutes after application onto the nerve roots (fold expression: IL-1[beta]; 13.47 [+ or -] 3.03, TNF 2.89 [+ or -] 2.08, Csf1; 3.13 [+ or -] 1.21).
Interestingly, the NP-induced changes in expression were almost completely blocked when NP was applied together with minocycline, the inhibitor of glial cells and macrophage activation (fold expression: IL1[beta]; 5.19 [+ or -] 2.08, TNF; 1.55 [+ or -] 0.43, Csf1; 0.92 [+ or -] 0.15, CX3CL1; 2.01 [+ or -] 0.51, CX3CR1; 1.95 [+ or -] 0.45).
Based on cytogenetic and molecular findings, most tumors appear to be clonal, neoplastic proliferations driven by CSF1
production of the neoplastic cells, which account for only a small percentage of the cell population in TSGCT.
One of the important factors that control the microglia population are the signals emanating from the binding of colonystimulating factor 1 (CSF1) and interleukin 34 (IL-34) to the microglial CSF1 receptor (CSF1R).
M2 macrophages secrete growth factors such as IGF-I, FGF, and CSF1, as well as neurotrophic factors such as NGF, BDNF, neurotrophin 4/5, and glial cell-derived neurotrophic factor (GDNF).
Inhibition of colony-stimulating factor-1 (CSF1
, also known as M-CSF), the primary regulator of tissue macrophage production, or the blockade of CSF-1 receptor (also known as CD115 or c-fms) led to decreased macrophage infiltration and less mammary tumor growth .
(170) A recent study189 suggests that dysregulation of several genes (FRA2, ID2, and the CSF1
receptor gene), through unknown mechanisms, may create conditions favorable for the occurrence of translocations and contribute to lymphomagenesis.
Besides, in pancreatic ductal adenocarcinoma, cancer cells secrete colony-stimulating factor 1 (CSF1
) to attract and stimulate CSF1
receptor- (CSF1R-) expressing TAM to express high levels of cytidine deaminase (CDA), an intracellular enzyme which catabolizes the bioactive form of gemcitabine and therefore protects the cancer cells from the chemotherapy .
Wang et al., "Injured sensory neuron-derived CSF1
induces microglial proliferation and DAP12dependent pain," Nature Neuroscience, vol.
Tumour cells produce CSF1
that induces EGF expression in TAMs.
The data indicated that the expression of over 50 human genes, such as SMAD6, CSF1
, VCAM-1, and TSG-6, was upregulated.