Scinderin: a metastasis-associated biomarker identified in metastatic lung nodule interstitial fluid proteomics

The tumor microenvironment is a critical factor in understanding cancer progression and metastasis. In this context, isolating tumor interstitial fluid (TIF) is a powerful tool for detecting cancer biomarkers and therapeutic targets. In our study, we conducted a proteomic analysis of TIFs from metastatic lung nodules using a murine model. The TIFs from these lungs were enriched with actin-binding proteins, among other molecules. Notably, we identified Scinderin (Scin), an actin-binding protein secreted by tumor cells. Knockdown of Scin resulted in a significant decrease in the number and size of lung nodules, as well as a reduction, albeit to a lesser extent, in disseminated tumor cells (DTCs). Furthermore, silencing Scin inhibited cell and tumor growth in different cancer cell lines. In human tumors, Scin was detected in the tumor interstitial fluid (TIF) of endometrial cancer patients. Scin was expressed abundantly in serous endometrial carcinomas and in the secretory endometrium. Remarkably, a paired analysis using an endometrial cancer tissue-array revealed increased Scin expression in metastatic samples compared to their corresponding primary tumors. In addition, a retrospective study revealed that levels of Scin in plasma were significantly elevated in patients who developed metastases. These findings suggest that Scin plays a significant role in the metastatic process and may serve as a promising biomarker for tumor aggressiveness and metastatic potential.