Using 3D Invasion properties of RCC Cell Lines In Vitro to predict their Metastatic Potential In Vivo

TL;DR

This study uses 3D cell models to predict how aggressive different kidney cancer cell lines are in spreading to other parts of the body.

Contribution

The study introduces 3D invasion models that accurately predict RCC metastasis in vivo using in vitro cell behavior.

Findings

RCC7 and 786-O cell lines showed higher metastatic potential compared to RCC10 in zebrafish and mouse models.

3D spheroid and tumoroid models accurately predicted in vivo metastatic behavior of RCC cell lines.

RCC7 exhibits partial epithelial-mesenchymal transition and upregulates metastatic markers.

Abstract

Renal cell carcinoma (RCC) exhibits significant heterogeneity, making it challenging to predict tumor aggressiveness and therapeutic response. To improve prognostic accuracy and develop tailored treatment strategies, it is crucial to mimic both cancer cells and their microenvironment in vitro. Using a combination of in vitro and in vivo models, we investigated the invasive properties of three RCC cell lines, RCC10, RCC7 and 786-O, that displayed distinct signaling profiles, combining EMT characteristics and upregulation of key metastatic markers. Our findings revealed that RCC7 and 786-O exhibited greater metastatic potential than RCC10, as demonstrated by increased extravasation in zebrafish embryos and higher lung metastases in the chorioallantoic membrane (CAM) and mice models. Comparative pathway analysis indicated that RCC7 displays partial epithelial-mesenchymal transition (pEMT) characteristics and upregulates key metastatic markers. Furthermore, our 3D spheroid invasion model as well as our patient-derived RCC tumoroid system predicted accurately their metastatic behavior, closely mirroring their aggressiveness in vivo. Thus, these 3D models might be predictive of tumor outcome, underscoring their utility as reliable predictive tools for RCC progression and therapeutic response.

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