Studies have shown that several types of cancer overexpress neurotrophins such as NGF and BDNF, which might contribute to tumor progression and angiogenesis.
Previous progress has indicated that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), two NTF family members, may be involved in the process of tumor progression.
The GNC-siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects.
TrkAIII antagonizes NGF/TrkAI signaling, which is responsible for NB growth arrest and differentiation through Ras/MAPK, and its expression is promoted by hypoxia at the expense of NGF-responsive receptors, providing a mechanism for converting NGF/TrkA/Ras/MAPK antioncogenic signals to TrkAIII/IP3K/Akt/NF-kappaB tumor-promoting signals during tumor progression.
Altered expression and activation of the nerve growth factor receptors TrkA and p75 provide the first evidence of tumor progression to effusion in breast carcinoma.
A loss of activation of the NGF/TrkA pathway occurs during tumour progression and may contribute to loss of tumour differentiation in esophageal cancer.
In conclusion, the present work reports that a NGF-mediated autocrine loop with an inhibitory role in the control of cell proliferation and tumor progression is active in the more differentiated DA-sensitive prolactinoma cell lines and is lost in the most malignant prolactinoma cells refractory to the dopaminergic therapy.