Cutaneous squamous cell carcinoma (cSCC) is the most prominent tumor of non-melanoma skin cancers and the most aggressive tumor among keratinocyte carcinoma of the skin, showing a high potential for local invasion and metastasis. The cSCC incidences increased dramatically in recent years and the disease occurs more commonly than any other malignancy. The secretome of cancer cells is currently the focus of many studies in order to identify new marker proteins for different types of cancer and to investigate its influence on the tumor microenvironment. In our study we evaluated whether the secretome of cSCC cells has an impact on keratinocytes, the surrounding tissue cells of cSCC. Therefore, we analyzed and compared the secretome of human A431 cancer cells and of HaCaT keratinocytes by mass spectrometry. In a second experiment, keratinocytes were exposed to the secretome of A431 cells and vice versa and the transcriptome was analyzed by next-generation sequencing. HaCaT cells incubated with A431 conditioned medium revealed a significantly activated mammalian target of rapamycin pathway with a concomitant increase in proliferation and migration. In conclusion, our data demonstrate the impact of the secretome of cancer cells on the transcription machinery of the cells surrounding the tumor, leading to a tumorigenic cell fate.

中文翻译：

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皮肤癌细胞的分泌组激活健康角质形成细胞中的mTOR / MYC途径并诱导致瘤性。

皮肤鳞状细胞癌（cSCC）是非黑色素瘤皮肤癌中最突出的肿瘤，也是皮肤角质形成细胞癌中最具侵略性的肿瘤，显示出局部浸润和转移的高潜力。近年来，cSCC发生率急剧上升，该疾病的发生率比任何其他恶性肿瘤都高。癌细胞的分泌组目前是许多研究的重点，目的是鉴定针对不同类型癌症的新标记蛋白，并研究其对肿瘤微环境的影响。在我们的研究中，我们评估了cSCC细胞的分泌组是否对cSCC周围组织细胞角质形成细胞有影响。因此，我们通过质谱分析和比较了人A431癌细胞和HaCaT角质形成细胞的分泌组。在第二个实验中 将角质形成细胞暴露于A431细胞的分泌组，反之亦然，并通过下一代测序分析转录组。用A431条件培养基孵育的HaCaT细胞显示出雷帕霉素途径的哺乳动物活化靶，伴随增殖和迁移的增加。总之，我们的数据证明了癌细胞的分泌组对肿瘤周围细胞转录机制的影响，从而导致了致瘤细胞的命运。