Objective
The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant lesions.
Materials and Methods
Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06.
Results
The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p<0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; p<0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; p=0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high
(p<0.05) and CD31high/SDF1high
(p=0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions.
Conclusion
The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant lesions and may hence be used in identifying high-risk OPMD.
1. Apart from conferring multidrug resistance to cancer cells, P-glycoprotein (P-gp) encoded by the gene ABCB1 (also, known as Multidrug resistance gene, MDR1), plays a major role in drug disposition. Single nucleotide polymorphisms (SNPs) in the ABCB1 gene might contribute to inter-individual and ethnic differences in drug disposition and thereby, could influence the outcome and prognosis of certain diseases. 2. India is one of the most ethnically and genetically diverse regions of the world. This study was undertaken with a view to determine the allele and genotype frequencies of C3435T and C1236T polymorphisms in the ABCB1 gene among the Maharashtrian population, residing in the Vidarbha region of central India and compare them with HapMap and other Indian populations. The common synonymous C3435T polymorphism has been found to be associated with lower P-gp functional expression and drug uptake, alone or in conjunction with a few other linked SNPs like C1236T. 3. The genotypes of C3435T and C1236T SNPs were determined by PCR-RFLP in 222 healthy and unrelated Maharashtrian individuals. 4. According to the findings of this study, the Maharashtrians were found to be not significantly different from the Gujarati Indians in Houston, Texas in the HapMap database.
Exposure of bitumen extract to HOS cells results in the cellular transformation similar to cancer cells and can modulate proteins involved in the progression of cancer. We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein.
The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.