Automatic tool for analysis of morphometric changes in the tumor spheroids regions treated with cisplatin

Abstract

Abstract Spheroids provides an in vitro cell culture model that mimics cancer cell growth in the in vivo solid tumor microenvironment. This cell culture model has revolutionized drug response studies. The architecture of the spheroid allows the cells to form different layers depending on oxygen, nutrients, and pH gradients. These layers, called proliferative, quiescent, and necrotic zones, are relevant in the treatment response evaluation because the cells present there have different behavior, which provides a better approach to evaluate treatments that can be correlated to in vivo response. Consequently, a key aspect for evaluation in this culture type is to analyze its morphology features; this is added to the main problem in extracting all parameters necessary for analysis. To overcome this difficulty, in this work, we proposed a MATLAB script for analyzing layers or zones of CAL27 spheroids with automatic computation of different morphological parameters. We correlated with in vitro experiments to improve the development and evaluation of antitumor drugs. This analysis utilizes inverted microscopy imaging of squamous oral carcinoma cells growing in spheroids treated or untreated with cisplatin. We developed and tested a software tool that detects each zone of the spheroid from threshold values and the changes in treatment response. The morphological parameters sphericity and solidity changes were observed in spheroids treated and untreated with cisplatin 20µM in the different zones. Besides, we observed that the quiescent zone was increased after treatment.