Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro.
After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments.
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. kemeny.lajos@gmail.com.
Lajos V
LV
Kemény
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. kurgyis.zsuzsanna@med.u-szeged.hu.
Zsuzsanna
Z
Kurgyis
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. buknicz.tunde@med.u-szeged.hu.
Tünde
T
Buknicz
MTA-SZTE Dermatological Research Group, Szeged 6720, Hungary. groma.gergo@gmail.com.
Gergely
G
Groma
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. yakoo@freemail.hu.
Ádám
Á
Jakab
Institute of Immunology &amp; Experimental Oncology, Witten/Herdecke University, Witten 58453, Germany. kurt.zaenker@uni-wh.de.
Kurt
K
Zänker
Institute of Immunology &amp; Experimental Oncology, Witten/Herdecke University, Witten 58453, Germany. thomas.dittmar@uni-wh.de.
Thomas
T
Dittmar
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. kemeny.lajos@med.u-szeged.hu.|MTA-SZTE Dermatological Research Group, Szeged 6720, Hungary. kemeny.lajos@med.u-szeged.hu.
Lajos
L
Kemény
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary. nemeth.istvan.balazs@med.u-szeged.hu.
István B
IB
Németh
D015415:Biomarkers; D018929:Cell Culture Techniques; D002459:Cell Fusion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006822:Hybrid Cells; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers
cell fusion; fibroblast; macrophage; spontaneous melanoma