Homeostatic Imbalance in Epithelial Ducts and Its Role in Carcinogenesis

Katarzyna A Rejniak

doi:10.6064/2012/132978

Abstract

An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis) of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones). However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas). Using the previously developed biomechanical model of epithelial ducts: IBCell, we investigated how different signals and mechanical stimuli imposed on individual epithelial cells can impact the homeostatic (im)balance and integrity of the whole epithelial tissue. We provide a link between erroneous responses of individual epithelial cells to specific signals and the emerging ductal morphologies characteristic for preinvasive cancers observed in pathology specimens, or characteristic for multicellular structures arising from mutated cells cultured in vitro. We summarize our finding in terms of altered properties of epithelial cell polarization, and discuss the relative importance of various polarization signals on the formation of tumor-like multicellular structures.

Highlights

Epithelia are one of the most abundant tissues in the human body and cover all cavities and surfaces of many organs, including the bronchi and alveoli of the lungs, breast ducts and lobules, gastrointestinal crypts, reproductive urinary tracts, and the endocrine glands
All critical decisions regulating epithelial tissue integrity, such as initiation of cell growth, selection of the axis of cell division, or the induction of cell death, may be in uenced by actions of neighboring cells and interactions between the cells and their dynamically evolving microenvironment. is includes diverse set of forces, such as compressive, tensile, or hydrostatic pressures, each of which plays a part in shaping the tissue [1,2,3]. e way in which cells respond to forces is dictated by their physical properties
Scienti ca remodeling is the process of involution—a programmed destruction and removal of the breast epithelial ducts that were generated during pregnancy to enable milk production. is postlactation regression involves a massive death of epithelial cells and remodeling of epithelial ducts to their prepregnant state and function [28]

Summary

Introduction

Epithelia are one of the most abundant tissues in the human body and cover all cavities and surfaces of many organs, including the bronchi and alveoli of the lungs, breast ducts and lobules, gastrointestinal crypts, reproductive urinary tracts, and the endocrine glands. In IBCell, epithelial polarity is acquired by developing three distinct membrane compartments (Figure 1): basal, de ned by cell membrane receptors contacting the external media (red); lateral, de ned by cell receptors being in contact with other cells (green); apical, composed of markers facing the hollow lumen (cyan).

Results

Conclusion