Title:Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy
Volume: 22
Issue: 1
Author(s): Shahram Taeb, Milad Ashrafizadeh, Ali Zarrabi, Saeed Rezapoor, Ahmed Eleojo Musa, Bagher Farhood and Masoud Najafi*
Affiliation:
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
Keywords:
Radiotherapy, cancer stem cells, tumor microenvironment, cancer-associated fibroblasts, extracellular matrix, hypoxia- inducible factor.
Abstract: Cancer is a chronic disorder that involves several elements of both the tumor and the
host stromal cells. At present, the complex relationship between the various factors presents in the
tumor microenvironment (TME) and tumor cells, as well as immune cells located within the TME,
is still poorly known. Within the TME, the crosstalk of these factors and immune cells essentially
determines how a tumor reacts to the treatment and how the tumor can ultimately be destroyed, remain
dormant, or develop and metastasize. Also, in TME, reciprocal crosstalk between cancer-associated
fibroblasts (CAFs), extracellular matrix (ECM), hypoxia-inducible factor (HIF) intensifies
the proliferation capacity of cancer stem cells (CSCs). CSCs are a subpopulation of cells that reside
within the tumor bulk and have the capacity to self-renew, differentiate, and repair DNA damage.
These characteristics make CSCs develop resistance to a variety of treatments, such as radiotherapy
(RT). RT is a frequent and often curative treatment for local cancer which mediates tumor elimination
by cytotoxic actions. Also, cytokines and growth factors that are released into TME have
been involved in the activation of tumor radioresistance and the induction of different immune
cells, altering local immune responses. In this review, we discuss the pivotal role of TME in the resistance
of CSCs to RT.