Hormone Expression in Melanomas Related to Tumor Angiogenesis

Abstract

Background: Vicarious production of pituitary hormones by malignant tumors is a well-known phenomenon. Prolactin (PRL), human growth hormone (HGH), adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone (α-MSH) expression has been reported in malignant melanoma tumor cell lines. The present study examines the pattern of expression of the hormones ACTH, PRL and HGH in melanoma with regard to tumor growth and differentiation in relation to angiogenesis. Methods:During angiogenesis the tumor cells encircle a central vessel in layers to form a tumor-vascular-complex (TVC) with a central vessel and a mantle of 5 to 6 layers. Hormone expression is assessed by immunopositivity for PRL, HGH, and ACTH in the tumor-vascular complexes, on serial frozen and paraffin sections and subjected to statistical analysis (t-test or Mann-Whitney U-test). Results:As two layers accrue the tumor cells acquire PRL and HGH positivity and are associated with a wave of mitotic activity in these layers. Further addition of layers shows ACTH positivity in the outer layers in association with pigmentation.Discussion: There is a coordinated growth of melanoma cells around neovascular channels, the cell cycle of malignant melanocytes being orchestrated by the three pituitary hormones, PRL, HGH and ACTH. The expression of PRL and HGH is related to mitotic activity while ACTH and pigment indicate differentiated function.

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] …”

Extracellular matrix proteins, neural differentiation and melanoma progression

“…In the developing embryo, for example, they play vital roles in early and late morphogenetic processes, including blastomere formation [6] . In the vertical growth phase (VGP) melanomas, tumor vascular interaction at the infiltrating margins results in the formation of tumor vascular complexes (TVCs) which show organized neural differentiation [7][8][9] . The present work utilizes the in situ 3D tumor matrix of melanomas to study the role of Ln5 and integrin α5β1 in TVC formation, tumor invasion and vasculogenesis.…”

Gangliosides and Antigangliosides in Malignant Melanoma

“…Gangliosides influence anticancerous therapy through several mechanisms [51,[79][80][81][82][83][84][85] i) overexpression of proangiogenic factors; ii) functional mutations in tumor suppression genes; iii) overexpression of some oncogenes conferring resistance to hypoxia, and though instability of genes and inhibition of apoptosis; iv) impaired detoxification and DNA repair mechanisms; v) mutations of endothelial cells; vi) selective activation of genes associated with melanoma resistance to apoptosis; vii) cells inability to accumulate sphingosine, sphingaanine and ceramide; viii) ability of melanoma cells to acetylate gangliosides.…”