Identifying Cell Differentiation in Colorectal Cancer

Abstract

The intestinal epithelium is a rapid self-renewing tissue. Stem cells at the bottom of the crypts first give rise to a proliferative progeny that finally differentiates to a variety of cell types. These terminally differentiated intestinal cells are mostly present in the villi of the intestinal wall and serve as functional units to sustain the main purpose of the organ: food absorption. But for a balance homeostasis, the intestine is composed not only by absorptive enterocytes but also by other cell types such as goblet cells that secrete mucus to lubricate the intestinal lumen, Paneth cells that secrete antimicrobial peptides to control microbiome, and others. Many relevant conditions affecting the intestine including chronic inflammation, Crohn’s disease, or cancer can alter the composition of these different functional cell types. As a consequence, they can lose their specialized activity as functional units and further contribute to disease progression and malignancy. Measuring the amount of these different cell populations in the intestine is essential to understand the bases of these diseases and their specific contribution to their malignancy. Interestingly, patient-derived xenograft (PDX) models faithfully recapitulate patients’ tumors including the proportion of the different cell lineages present in the original tumor. Here we expose some protocols for evaluating the differentiation of intestinal cells in colorectal tumors.