Biogenic amines and tumor-vascular interaction in melanomas

Abstract

BackgroundIn nodular melanomas in vertical growth phase, tumor-vascular complexes (TVC), with perivascular mantle zone (PMZ) of 5 to 6 layers (L1-L5) of tumor cells are formed around angiogenic vessels at the tumor-stroma interphase, showing organized neural differentiaton. The present study explores the sequence of biogenic amines positivity in relation to angiogenesis, utilizing the TVC as a 3D model. MethodsThe sequence of positivity for Nestin (Nes), GFAP, indoleamines: serotonin (SER)/melatonin (MLT), catecholamines: dopamine (DA)/noradrenalin (NA), pigment (Pig); dopa oxidase (DO); and related mitosis in layers of the PMZ (L1-L5) was assessed in 897 developing TVCs using 5 µm serial paraffin and frozen sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures (Tukey Test). Results Nes, GFAP appear in L1/L2, next indoleamines (serotonin/melatonin) in L2/L3 associated with mitosis. DA is positive in L3/L4 coinciding with DO which peaks in L4 with NA, Pig appears in L4/L5. Mitosis in L2/L3 is associated with indoleamine positive cells which remain in L2/L3, with catecholamine positive cells moving into L4/L5 thus establishing a polarity. Conclusion Thus, the angiogenic vessel confers polarity and an embryonal microenvironment in the PMZ, the aggressive melanoma cells functioning as neuronal stem cells to resemble early neurogenesis of bio-aminergic cells.

Tumor Vascular Interaction in Melanomas and Neurogenesis: A Review

“…The above findings correlate with expression of neural markers as well as biogenic amines in the TVCs [12,21,66]. PRL/HGH positivity associated with mitosis, coincides with the appearance of indoleamines, the presence of melatonin indicating the effect of biophoton emissions during mitosis.…”

“…TVCs show organized expression of biogenic amines in relation to the angiogenic vessel in the middle layers (indoleamines) and in outer (catecholamines) coinciding with increasing Syn positivity [66]. On comparing the levels of positivity in the total number of TVC, GFAP positivity is seen in the layers adjacent to the vessel wall (L1-3).…”

Melanocyte-endothelial melanomas: Plasticity and transdifferentiation in melanomas

“…The presence of near normal mitosis, normal sequential neural differentiation as well as morphometric parameters (see Figure 4D) suggest that normal cells are involved. [17][18][19][20] It is difficult to accept that angiogenic endothelial tubes can normalize the highly pleomorphic melanoma cells so drastically on contact.…”

“…[3,16] There is a regimented differentiation in the TVCs, beginning with glial differentiation of the innermost layer of cells followed by expression of indoleamines [serotonin (L2: 71.8%; L3: 62.8%); melatonin (L2: 60.9%; L3: 64.1%)], hormones [PRL (L2: 42.5%; L3: 39.8%); HGH (L2/L3: 48.6%)] in the middle layers, associated with mitotic activity. [17][18][19][20] The outer layers express the neural markers NFP (L4: 52.2%; L5: 50.6%) and Syn (L4: 63%; L5: 64.1%); catecholamines: DA, (L3/4: 75%); NA (L3: 70%; L4: 80%; L5: 60%) enzyme DO (L4: 84.9%; L5: 96.9%), Pigment (L5: 60%). and ACTH (L4: 64.2%; L5: 61.6%) (see Figure 4C, a-c) [17][18][19] and are associated with very few mitotic figures.…”

“…[17][18][19][20] The outer layers express the neural markers NFP (L4: 52.2%; L5: 50.6%) and Syn (L4: 63%; L5: 64.1%); catecholamines: DA, (L3/4: 75%); NA (L3: 70%; L4: 80%; L5: 60%) enzyme DO (L4: 84.9%; L5: 96.9%), Pigment (L5: 60%). and ACTH (L4: 64.2%; L5: 61.6%) (see Figure 4C, a-c) [17][18][19] and are associated with very few mitotic figures. [20] …”