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.
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.
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.
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.
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.