Role of microenvironment in regulating stem cell and tumor initiating cancer cell behavior and its potential therapeutic implications

Abstract

Microenvironment plays a key role in controlling stem cell fate and thereby regulating tissue homeostasis and repair. It consists of acellular and cellular components that interact with stem cells and their progenitors and through signaling cascades infl uence balance between self-renewal, differentiation and dormancy. Under pathological conditions, disruptions in microenvironment can generate signals that stimulate untimely or aberrant stem cell differentiation or self-renewal, or activate de-differentiation of progenitor cells, leading to diseased states such as cancer. However, while unaltered microenvironment can restrain transformed cell behavior inhibiting malignant phenotypes, transformed cancer cells that exhibit resistance to conventional therapies and tumor initiating capacity are capable of inducing more permissive and immunotolerant microenvironment that promotes tumor growth and metastasis. Better understanding of their behavior and interactions with microenvironment opens up novel avenues for devising more effi cacious cancer therapies.