InvasiCell is a physiologically relevant in vitro model for the study of tumor progression and the evaluation of potential cancer medications more accurately than current in vitro assays

Abstract

Cancer cases have been constantly increasing over the past few decades, leading it to become the second cause of lethality worldwide, with cancer metastasis being responsible for approximately 90% of cancer-related deaths. Thus, cancer research is essential to enhance our knowledge of the underlying mechanisms that drive tumor progression and metastasis in order to enable the development of new anti-cancer therapies. However, even though in vivo and in vitro models that are currently used in cancer research have provided valuable information on cancer progression, only a few therapies that show promise in vitro studies eventually prove efficacious in clinical studies. Consequently, several studies emphasize the limitations of in vitro models, which are currently used in cancer research, and highlight the need for the development of new more physiologically relevant in vitro models for the study of tumor progression and evaluating the efficacy of potential new anti-cancer medications. The aim of this study was to examine whether InvasiCell, a novel device and associated in vitro assay that were developed in our lab, can be used as a physiologically relevant model to study various aspects of tumor progression, compared to the existing in vitro tools that are currently used in cancer research. Specifically, wound healing assays, Boyden chamber assays, InvasiCell, and tumor spheroids, were used to evaluate the in vitro invasive potential of previously characterized breast and pancreatic cancer cell lines with known in vivo metastatic potential. The collective data from this study suggest that InvasiCell reflects the in vivo metastatic potential of the evaluated cell lines more accurately and reliably than other assays. Additionally, given that fibroblasts are the most abundant stromal cell type in the tumor microenvironment and their role in tumor progression is controversial, we used InvasiCell to examine whether the presence of NIH3T3 fibroblasts could affect tumor cell invasive capacity and potentially improve our ability to predict the metastatic potential of tumor cells. Our findings indicate that the inclusion of fibroblasts with cancer cells reduces the invasion potential of various breast cancer cell lines tested. Finally, to examine if InvasiCell could be used as a drug response assay, we treated breast cancer cell lines with previously established concentrations of Doxorubicin Hydrochloride under normal tissue conditions or within InvasiCell. We observed that the cells within InvasiCell displayed enhanced drug resistance, which resembles previously published studies performed with spheroid assays. Collectively, InvasiCell can effectively distinguish cell lines with different metastatic capacities, allow researchers to examine tumor cell behavior and interactions by performing co-culture experiments with other cell types, and study cellular resistance to various drugs. Therefore, InvasiCell is a promising tool for cancer research, which could enhance our knowledge and understanding of critical steps in tumor progression and facilitate the development of more effective anti-cancer strategies and therapies.