Engineering 3D Organotypic Models for the Study of Breast Cancer Metastasis

Abstract

Breast cancer is the most common form of cancer among women the world over. Metastasis, or, the spreading of the primary tumor to other vital organs, is the major cause of mortality in breast cancer. Metastasis is a multi-step process wherein the cancer cells migrate from the primary tumor through the vasculature and lymphatics to other sites such as lung, brain and bone and establish a secondary tumor at that site. Understanding the molecular mechanisms that orchestrate metastasis can provide useful insights into developing therapeutics that prevent or treat metastasis. While culturing cancer cells in conventional two-dimensional (2D) cell culture systems fail to mimic in vivo signaling due to the planar architecture and inappropriate substrate stiffness, animal based xenograft models of metastasis are expensive and time consuming. To overcome these drawbacks, three-dimensional (3D) scaffold based models have been developed that recreate the in vivo tissue microenvironment. The aim of this work was to develop models to study breast cancer biology using 3D scaffolds that would overcome the disadvantages of the animal models and 2D culture systems and better mimic the tumor in vivo