*Article* **MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy**

**Silke Schrom <sup>1</sup> , Thomas Hebesberger <sup>1</sup> , Stefanie Angela Wallner <sup>1</sup> , Ines Anders <sup>1</sup> , Erika Richtig <sup>2</sup> , Waltraud Brandl <sup>3</sup> , Birgit Hirschmugl 3,4, Mariangela Garofalo <sup>5</sup> , Claudia Bernecker <sup>6</sup> , Peter Schlenke <sup>6</sup> , Karl Kashofer <sup>7</sup> , Christian Wadsack 3,4 , Ariane Aigelsreiter <sup>7</sup> , Ellen Heitzer <sup>8</sup> , Sabrina Riedl 4,9,10 , Dagmar Zweytick 4,9,10, Nadine Kretschmer <sup>11</sup>, Georg Richtig <sup>12</sup> and Beate Rinner 1,4,\***

	- Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine,

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**Abstract:** Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapyresistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is challenging to treat. The aim of this study was to provide a potential model system for the study of melanoma in pregnancy and to illustrate melanoma heterogeneity. For this purpose, a pigmented and a non-pigmented section of a lymph node metastasis from a pregnant patient were cultured under different conditions and characterized in detail. All four culture conditions exhibited different phenotypic, genotypic as well as tumorigenic properties, and resulted in four newly established melanoma cell lines. To address treatment issues, especially in pregnant patients, the effect of synthetic human lactoferricin-derived peptides was tested successfully. These new *BRAF*-mutated MUG Mel3 cell lines represent a valuable model in melanoma heterogeneity and melanoma pregnancy research. Furthermore, treatment with anti-tumor peptides offers an alternative to conventionally used therapeutic options—especially during pregnancy.

**Keywords:** melanoma; tumor heterogeneity; pregnancy; anti-tumor peptides; in vitro model
