title: Cultivation-dependent plasticity of melanoma phenotype.
abstract: Malignant melanoma is a highly aggressive tumor with increasing incidence and high mortality. The importance of immunohistochemistry in diagnosis of the primary tumor and in early identification of metastases in lymphatic nodes is enormous; however melanoma phenotype is frequently variable and thus several markers must be employed simultaneously. The purposes of this study are to describe changes of phenotype of malignant melanoma in vitro and in vivo and to investigate whether changes of environmental factors mimicking natural conditions affect the phenotype of melanoma cells and can revert the typical in vitro loss of diagnostic markers. The influence of microenvironment was studied by means of immunocytochemistry on co-cultures of melanoma cells with melanoma-associated fibroblast and/or in conditioned media. The markers typical for melanoma (HMB45, Melan-A, Tyrosinase) were lost in malignant cells isolated from malignant effusion; however, tumor metastases shared identical phenotype with primary tumor (all markers positive). The melanoma cell lines also exerted reduced phenotype in vitro. The only constantly present diagnostic marker observed in our experiment was S100 protein and, in lesser extent, also Nestin. The phenotype loss was reverted under the influence of melanoma-associated fibroblast and/or both types of conditioned media. Loss of some markers of melanoma cell phenotype is not only of diagnostic significance, but it can presumably also contribute to biological behavior of melanoma. The presented study shows how the conditions of cultivation of melanoma cells can influence their phenotype. This observation can have some impact on considerations about the role of microenvironment in tumor biology.
authors.affiliation: 1st Faculty of Medicine, Department of Dermatovenereology, Charles University, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Kodet
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvořánková
authors.forename: Eliška
authors.initials: E
authors.lastname: Krejčí
authors.forename: Pavol
authors.initials: P
authors.lastname: Szabo
authors.forename: Petr
authors.initials: P
authors.lastname: Dvořák
authors.forename: Jiří
authors.initials: J
authors.lastname: Štork
authors.forename: Ivana
authors.initials: I
authors.lastname: Krajsová
authors.forename: Pavel
authors.initials: P
authors.lastname: Dundr
authors.forename: Karel
authors.initials: K
authors.lastname: Smetana
authors.forename: Lukáš
authors.initials: L
authors.lastname: Lacina
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D058965:MART-1 Antigen / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects; D058951:gp100 Melanoma Antigen
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; D058965:MART-1 Antigen; D058950:Melanoma-Specific Antigens; D064231:Nestin; C548637:PMEL protein, human; D009418:S100 Proteins; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase