Of the 154 melanoma samples, 77 (55.4%) were TrkA immunopositive, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, and 104 (75.4%) were NGF immunopositive.
Malignant transformation of melanomas is accompanied by loss of KIT and acquisition of EPO-R and ErbB4, both of which are co-expressed with NGF-R and PD-1 in distinct subfractions of melanoma cells.
Transcripts of c-myb and the beta-NGF gene were not detectable in any of the melanoma cell lines, whereas sis- and epidermal growth factor (EGF) receptor gene-specific transcripts were present in two and four melanoma cell lines, respectively.
In the absence of p140proto-trkA, the matrix-dependent effects of NGF on metalloproteinase expression of brain-metastatic 70W melanoma cells suggest a signaling role for the low-affinity melanoma p75NTR receptor and its associated purine-analogue-sensitive kinase in signaling enhanced matrix penetration of NGF-rich stromal microenvironments such as the brain.
The molecular mechanism by which NGF and PDGF affect growth of tumor cells was tested in human melanoma WM 266-4 and colorectal carcinoma SW 707 cell lines.