Epithelial PC cells, however, acquire the ability to express NGF and TrkA, as the disease progresses, indicating a role for NGF/TrkA axis in PC progression and androgen-resistance.
We observed the following: i) TrkA and TrkB expression was significantly higher in AR-negative compared to AR-positive cells; ii) TrkA and TrkB expression was related to the invasive capacity/malignancy of PCa cells; iii) p75 NGFR could be considered a tumor suppressor gene which is present at high levels only in AR-positive cells; and iv) that NGF and BDNF (targeting TrkA/p75 NTR and TrKB, respectively) induced cell migration and this was inhibited by the CEP-701 treatment.
We exposed the androgen-independent/androgen receptor (AR)-negative prostate cancer cell line DU145 to NGF to study whether this neurotrophin could revert DU145 cells to a less malignant phenotype.
These studies demonstrated that normal prostatic tissue from patients without prostate cancer contains substantial levels of nerve growth factor (NGF), which is produced in a paracrine manner by stromal cells.
However, the absence of mutations in otherwise genetically unstable prostate tumor DNA suggests that intact NGF/TrkA pathways may be important in prostate cancer development.