Tissue diagnosis using software-supported assessment of biomarkers

我们研究的总体目标是分析导致皮肤黑色素瘤发展的分子机制，以开发生物标志物和创新的治疗方法。所有这些方面都包括在这个建议中。我们之前的研究结果显示，激活的ADAM10可能在许多形式的皮肤黑色素瘤中发挥重要作用，基于体外对黑色素瘤细胞系信号通路的分析。在最近发表的一项研究中，我们可以在黑色素瘤组织中验证这一发现，并描述ADAM10激活的机制。我们发现内肽酶SPPL3是ADAM10的一个重要上游激活因子。使用所谓的MELC（多表位配体制图）技术在这种方法中至关重要。该技术允许在一个组织/细胞层及其地形定位内评估100多种不同的抗原。在本提案中，我们的目标是分析我们的发现和生物标志物是否可以应用于其他形式的皮肤黑色素瘤，以及是否可以通过图像分析软件支持的MELC技术将鉴定的组织生物标志物图谱用于组织诊断。此外，我们还将研究早期肿瘤微环境在ADAM10激活中的作用。

The overall goal of our research is to analyze the molecular mechanisms leading to the development of cutaneous melanoma, in order to develop biomarker profiles and innovative therapeutic approaches. All these aspects were included in this proposal.Our previous results revealed that activated ADAM10 may play an important role in many forms of cutaneous melanoma, based on the analysis of signaling pathways in melanoma cell lines in vitro. In a recently published study we could verify this finding in melanoma tissue and describe the mechanism of ADAM10 activation. We discovered that the endopeptidase SPPL3 acted as a crucial upstream activator of ADAM10. Using the so-called MELC (multi epitope ligand cartography) technology was crucial in this approach. This technology allows the assessment of more than 100 different antigens on one tissue/cell layer and within their topographical localization. In this proposal we aim to analyze whether our findings and biomarkers could be applied to other forms of cutaneous melanoma and if the identified tissue biomarker profiles could be used for tissue diagnosis by means of the MELC technology, powered by an image analysis software. Furthermore, the role of the early tumor microenviroment in ADAM10 activation will be investigated.