Research Summary

Understanding the biology of stem-like cancer cells from human oral tumors

Oral cancer is one of the deadliest cancers in Indian population. Stem-like cancer cells are believed to be associated with aggressive behaviour of cancer and therefore needs to be investigated in Oral cancer. The existence of oral stem-like cancer cells (Oral-SLCCs) has been challenged because of ambiguity in its identification. This project has undertaken the challenge of accurate identification of Oral-SLCCs directly from the tumor samples. We will strongly confirm that side-population cells are enriched with Oral-SLCCs and can be directly isolated from individual tumors. 

Given the high mutation rate in cancers, genomic heterogeneity among Oral-SLCCs within individual tumor will be examined. Functional implication of this diverse genomic makeup will next be tested. Isolated Oral-SLCCs will be plated as single cell to obtain monoclonal-cultures of Oral-SLCCs. Through in vitro assays we will be characterizing these monoclonal-cultures for their specific function. Mutation data at whole-genome level for these functionally characterized cultures will be generated. We anticipate to obtain distinct sets of mutated genes to be involved in conferring these two diverse functions. The causative role of mutated genes will next be assayed to strongly demonstrate the specific impact of these mutations in providing a definite and distinct role to diverse Oral-SLCCs.

Figure Legend: This diagram depicts our current understanding about stem cell model of cancer. Normal tissue stem cells with intrinsic properties of self-renew and multi-lineage differentiation acquire the oncogenic mutations which results in its deregulated self-renewal and give rise to cancer stem cells. Additionally, mutations might also cause restricted progenitor cells to acquire cells self-renewal property and become malignant stem-like cancer cells. These cells self-renew themselves as well as differentiate to generate phenotypically diverse non-tumorigenic cancer cells, which constitute the bulk of the heterogeneous tumor. During cancer progression stem- like cancer cells may evolve and change in genotype and phenotype to produce subclonal heterogeneity. Evidences are also accumulating to demonstrate the reversal of mature cancer cells to re-acquire the stem like properties through de-differentiation.