226
11.6 Conclusion and Prospective
The molecular crosstalk between cancer stem cells and tumor microenvironment
play an important role in formation of intratumoral heterogeneity to modulate tumor
progression in oral cancer. TME accommodates cancer cells including CSCs and
creates an immunosuppressive atmosphere that safeguards CSCs from various
genetic and epigenetic offenses. Tumor niches are discrete domains that assure spe-
cific functional characteristics and encourage the formation of suitable microhabitat
for CSCs to maintain its stemness, invasiveness, metastatic proficiency, tumorige-
nicity and therapy resistance properties. Moreover, specific stimuli including
hypoxia, autophagy, tumor metabolism and tumor associated stromal cells in the
microenvironment stimulate reprogramming of signaling pathways in the way to
acquire stem-like characteristics. In HNSCC, CSCs express specific receptors, cyto-
kines and chemokines to recruit TAMs, promotes angiogenesis, differentiation of
MDSCs to TAMs to support immune evasion and tumor growth. In addition, CSCs
triggers extensive remodeling of ECM by inducing the degradation of matrix pro-
tein via various proteinases which facilitates invasion and metastasis. Although the
molecular interplay between CSCs and TME is well established, many cellular
events in this microhabitat remain unidentified. How CSCs especially circulating
tumor cells influence the stromal cells at new sites during metastasis and what is
molecular signaling for polarizing tumor associated cells? Does high autophagy
flux in CSCs associate intracellular antigen presentation to reprogram in generating
tumor promoting macrophages and other immune cells? It is also not known what is
the detail molecular circuit in establishing connection between CSCs and epidermal
keratinocytes during tumor progression in oral cancer. In conclusion, understanding
the CSCs and its tumor microenvironment with identification of key molecular
pathway might facilitate the development strategy to improve therapeutic outcomes
through precise intervention to treat oral cancer.
Acknowledgement Research support was partly provided by Department of Biotechnology
[Grant Number: BT/PR7791/BRB/10/1187/2013]; Science and Engineering Research Board
(SERB), Department of Science and Technology [Grant Number: SR/SO/BB-0101/2012]; Council
of Scientific and Industrial Research (CSIR) [Grant Number: 37(1608)/13/EMR-II] Human
Resource Development Group, Government of India; Science and Technology Department,
Government of Odisha. PPN is obliged to DST SERB, New Delhi, India for providing fellowship.
Conflict of Interest
The authors declare no conflicts of interest.
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