Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery

TLDR

Two‑dimensional cell cultures on plastic fail to recapitulate the three‑dimensional architecture and complexity of human tumors. More representative models are required for drug discovery and validation. The study established 2D culture and 3D mono‑ and stromal co‑culture models of increasing complexity using three standard carcinoma lines (MCF7, LNCaP, NCI‑H1437) and performed cross‑comparisons. Fluorescence‑based growth curves, 3D image analysis, immunohistochemistry, and treatment responses showed that endpoints differed by cell type, stromal co‑culture, and culture format, underscoring that the adaptable methodologies can guide the choice of appropriate simple and complex in‑vitro models.

Abstract

Abstract Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models.