Tumour Progression Stage-Dependent Secretion of YB-1 Stimulates Melanoma Cell Migration and Invasion.

Corinna Kosnopfel,Martin Schaller,Claus Garbe,Heike Niessner,Birgit Schittek,Peter R Mertens,Tobias Sinnberg,Alina Muenchow,Birgit Fehrenbacher,Birgit Sauer,Basant Kumar Thakur

doi:10.3390/cancers12082328

Abstract

Secreted factors play an important role in intercellular communication. Therefore, they are not only indispensable for the regulation of various physiological processes but can also decisively advance the development and progression of tumours. In the context of inflammatory disease, Y-box binding protein 1 (YB-1) is actively secreted and the extracellular protein promotes cell proliferation and migration. In malignant melanoma, intracellular YB-1 expression increases during melanoma progression and represents an unfavourable prognostic marker. Here, we show active secretion of YB-1 from melanoma cells as opposed to benign cells of the skin. Intriguingly, YB-1 secretion correlates with the stage of melanoma progression and depends on a calcium- and ATP-dependent non-classical secretory pathway leading to the occurrence of YB-1 in the extracellular space as a free protein. Along with an elevated YB-1 secretion of melanoma cells in the metastatic growth phase, extracellular YB-1 exerts a stimulating effect on melanoma cell migration, invasion, and tumourigenicity. Collectively, these data suggest that secreted YB-1 plays a functional role in melanoma cell biology, stimulating metastasis, and may serve as a novel biomarker in malignant melanoma that reflects tumour aggressiveness.

Highlights

The secretome of a cell represents the collective of all its factors released into the extracellular space
To evaluate a potential secretion of Y-box binding protein 1 (YB-1) from melanoma cells, conditioned serum-free cell culture supernatants were generated using a panel of melanoma cell lines as well as melanocytes (FM), keratinocytes (FK), and fibroblasts (FF) as benign control cells of the skin
The amount of secreted YB-1 seems to increase with melanoma progression from radial growth phase (RGP) over vertical growth phase (VGP) to the metastatic stage

Summary

Introduction

The secretome of a cell represents the collective of all its factors released into the extracellular space This includes extracellular matrix components, proteases, growth factors, cytokines, chemokines, as well as extracellular vesicles [1,2]. As an important pillar of cell–cell communication, these secreted factors can contribute to the acquisition and maintenance of the various cancer hallmarks defined by Hanahan and Weinberg in an autocrine, paracrine, or even endocrine manner [1,3,4,5]. This can happen by direct stimulation of tumour cell proliferation, survival, migration, and invasion. The adoption of pro-metastatic traits including mesenchymal properties and dedifferentiation of melanoma cells have been frequently described in therapy resistance [11,12,13]

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