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Tumor Discovery RAGEs in oral squamous cell carcinoma

IHC is used to study the distribution of these receptors increases the risk of OSCC . Allelic discriminations of
[19]
in tumor tissue sections, which revealed that 28% of the the RAGE rs1800625, rs1800624, rs2070600, and rs184003
articles studied the expression of RAGE in tumor tissues allelic polymorphisms were investigated, and it was
and the surrounding normal mucosa using IHC and observed that the RAGE gene polymorphism rs1800625
concluded that RAGE positivity is more prevalent at the not only raised the risk of oral cancer but was also related
invasive front and is expressed more in well-differentiated with late-stage and large-size tumors. The study also
than poorly differentiated OSCCs. This demonstrates sheds light on environmental factors that may alter RAGE
that the presence and activity of these receptors and their expression and oral cancer susceptibility. Even in the
ligands influence the invasiveness of tumor tissues. absence of tobacco chewing or smoking, polymorphism of

Vascular endothelial growth factor (VEGF) is the the rs184003 allele was found to predispose an individual
primary facilitator of tumor angiogenesis, encouraging the to a higher risk of oral squamous cell cancer. RAGE-
creation of new blood vessels from adjacent capillaries, and ligand antagonists may be able to effectively target the
granting tumors access to the oxygen and nutrients they “Achilles’ heel” of cancers, namely, poor prognosis, silent
require to flourish . VEGF also plays a crucial role in metastasis, drug resistance, and cancer recurrence, given
[12]
tumor development by protecting tumor neovasculature that inhibition of RAGE, HMGB-1, or S100 proteins alone
against apoptosis through the activation of anti-apoptotic has demonstrated a significant reduction in tumor size,
[13]
proteins Bcl-2 and survivin . The elevated amounts invasion, and angiogenesis in a number of cancers .
[20]
of VEGF in tumors also result in architecturally distinct In conclusion, there is promise for the creation of
blood vessels compared to normal blood vessels. In targeted therapeutics using RAGE products. Its potential
contrast to the architecture of normal vasculature, tumor significance in angiogenesis and tumor progression (cell
vasculature is irregularly formed, dilated, convoluted, invasion and motility) makes it an attractive adjuvant
and characterized by a large number of blind ends. Due
to the chaotic design of tumor vasculature, tumor blood therapy target. In vitro inhibition of RAGE signaling
flow is often poor, with areas of stasis caused by dead-end with RAGE antibodies decreased cell differentiation
arteries and disorganized blood flow caused by aberrant and migration, thereby establishing RAGE as a unique
vascular connections . This, in turn, predisposes regions and specific target for the treatment and management of
[13]
to hypoxia, which further stimulates VEGF release and OSCCs.
generates disorganized vasculature. In situ study of tumor 5. Conclusion
tissues undergoing neovascularization indicates the close
proximity of clusters of capillaries and VEGF-producing Despite insufficient understanding of the mechanism
cells to necrosis . of interaction between various ligands and families, the
[14]
In one of their articles, Sasahira et al. evaluated the available evidence supports the function of RAGE in
relationship between RAGE and VEGF, thereby anticipating invasion, migration, and angiogenesis in oral cancers. There
its role in angiogenesis [15,16] . Long recognized as the most has been no investigation on the diagnostic use of these
potent angiogenic factor, VEGF-A is frequently related markers for oral malignancies. Multiple clinicopathological
with increased MDV and unfavorable clinicopathological factors are associated with these oral cancer indicators.
characteristics and results . The expression of VEGF and This evidence is promising for the therapeutic application
[17]
VEGF-C was substantially correlated with MVD and LVD, of these compounds in prognostic considerations and
suggesting that RAGE also plays a role in angiogenesis. molecular target recognition treatment. To design a more
There was no association between VEGF and MVD targeted or possibly individualized treatment for patients,
numbers, either individually or in terms of grade . further study must be undertaken to acquire a better
[18]
knowledge of the molecular events.
Higher levels of AGE receptors were detected near the
invasive front of tumors, suggesting that these molecules Acknowledgments
play a role in the invasiveness and spread of cancers. These
results imply that these receptors and their associated None.
ligands play a significant role in the growth and spread
of the tumor, hence affecting the prognosis and life Funding
expectancy of the affected individual. None.
Su et al. examined the genetic predisposition for oral
squamous cell carcinoma; this investigation revealed that Conflict of interest
the presence of at least one polymorphic allele of rs1800625 The authors declare no conflicts of interest.

Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/td.244