Advancement in Cancer Stem Cell Biology and Precision Medicine—Review Article Head and Neck Cancer Stem Cell Plasticity and the Tumor Microenvironment

Abstract

Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor heterogeneity, treatment resistance, metastasis, and recurrence in solid malignancies including head and neck cancer. Initial studies identified cancer stem cell markers including CD44 and ALDH in head and neck malignancies and found that these cells show aggressive features in both in vitro and in vivo studies. Recent evidence has now revealed a key role of the tumor microenvironment in maintaining a cancer stem cell niche and promoting cancer stem cell plasticity. There is an increasing focus on identifying and targeting the crosstalk between cancer stem cells and surrounding cells within the tumor microenvironment (TME) as new therapeutic potential, however understanding how CSC maintain a stem-like state is critical to understanding how to therapeutically alter their function. Here we review the current evidence for cancer stem cell plasticity and discuss how interactions with the TME promote the cancer stem cell niche, increase tumor heterogeneity, and play a role in treatment resistance.

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“…Instead, a range of attributes in the CSC state is identified as a result of some CSC plasticity. In various cancer types, a “bidirectional interconversion” mode, i.e., the transition in daughter cells from stem to non-stem and non-stem to stem is constantly taking place [ 41 ]. Transition includes the de-differentiation of cancer cells towards stem-like phenotypes, ensuring the progression of cancer, and the multilineage differentiation of CSCs to increase genetic heterogeneity within the tumor mass [ 39 , 40 , 41 , 42 ].…”

“…In various cancer types, a “bidirectional interconversion” mode, i.e., the transition in daughter cells from stem to non-stem and non-stem to stem is constantly taking place [ 41 ]. Transition includes the de-differentiation of cancer cells towards stem-like phenotypes, ensuring the progression of cancer, and the multilineage differentiation of CSCs to increase genetic heterogeneity within the tumor mass [ 39 , 40 , 41 , 42 ]. Multilineage differentiation drives tumor growth and heterogeneity, and the heterogeneous, differentiated cancer cells form the bulk of the tumor [ 39 , 40 , 41 , 42 ].…”

“…Transition includes the de-differentiation of cancer cells towards stem-like phenotypes, ensuring the progression of cancer, and the multilineage differentiation of CSCs to increase genetic heterogeneity within the tumor mass [ 39 , 40 , 41 , 42 ]. Multilineage differentiation drives tumor growth and heterogeneity, and the heterogeneous, differentiated cancer cells form the bulk of the tumor [ 39 , 40 , 41 , 42 ]. Several different cell surface markers, including clusters of differentiation (CD) markers (e.g., CD24, CD133, and CD44), were shown in various cancers to be associated with CSC state and with aspect(s) of stem cell-like behavior [ 40 , 41 , 42 , 43 , 44 ].…”

“…Multilineage differentiation drives tumor growth and heterogeneity, and the heterogeneous, differentiated cancer cells form the bulk of the tumor [ 39 , 40 , 41 , 42 ]. Several different cell surface markers, including clusters of differentiation (CD) markers (e.g., CD24, CD133, and CD44), were shown in various cancers to be associated with CSC state and with aspect(s) of stem cell-like behavior [ 40 , 41 , 42 , 43 , 44 ].…”

“…An example is vasculogenic mimicry (VM), a hallmark process by which cells in the vicinity of CSCs transdifferentiate to acquire endothelial cell-like properties [ 45 ]. TME induces non-CSCs to obtain CSC properties, altering the trajectory of the non-stem subpopulation on malignant tumor growth [ 41 ]. TME also increases immune escape by inducing immune or stromal cells to secrete cytokines and exosomes and to activate stemness pathways in CSCs [ 45 ].…”