Molecular Mechanisms of Cancer Stem Cell Creation via High Nitric Oxide Adaptation
Session Number
C13
Advisor(s)
James Radosevich, University of Illinois at Chicago
Location
A-129
Start Date
28-4-2016 2:00 PM
End Date
28-4-2016 2:25 PM
Abstract
For some time, it has been known tumors exhibit morphological and functional heterogeneity. Multiple theories have been proposed to address the cause of this, the most accepted of which is the hierarchy model, which states that biologically distinct cell classes compose tumors and only one has the ability to initiate tumor growth: the cancer stem cell (CSC) class. Today, however, the origin of these CSCs is unknown and under active research. One hypothesis has been that CSCs are actually results of the adaptation of cancer cells to nitric oxide in high amounts (HNO). We replicated this adaptive process, exposing five adenocarcinoma (AC) and five squamous cell carcinoma (SCC) cell lines to HNO levels. Using genechip analysis, we observed the changes in gene expression in the cancers from this adaptation process. With various bioinformatic tools, we determined which genes were commonly up and downregulated across the ACs, the SCCs, and both the ACs and SCCs. The significant down-regulation of pyruvate dehydrogenase across all cell lines suggests that HNO- adapted cells go through a nonstandard pathway of cellular respiration. Furthermore, HNO-adapted SCCs displayed increased ribosomal production and genomic instability typical of CSCs. Our results clearly support the idea that CSCs are created from HNO- adaptation.
Molecular Mechanisms of Cancer Stem Cell Creation via High Nitric Oxide Adaptation
A-129
For some time, it has been known tumors exhibit morphological and functional heterogeneity. Multiple theories have been proposed to address the cause of this, the most accepted of which is the hierarchy model, which states that biologically distinct cell classes compose tumors and only one has the ability to initiate tumor growth: the cancer stem cell (CSC) class. Today, however, the origin of these CSCs is unknown and under active research. One hypothesis has been that CSCs are actually results of the adaptation of cancer cells to nitric oxide in high amounts (HNO). We replicated this adaptive process, exposing five adenocarcinoma (AC) and five squamous cell carcinoma (SCC) cell lines to HNO levels. Using genechip analysis, we observed the changes in gene expression in the cancers from this adaptation process. With various bioinformatic tools, we determined which genes were commonly up and downregulated across the ACs, the SCCs, and both the ACs and SCCs. The significant down-regulation of pyruvate dehydrogenase across all cell lines suggests that HNO- adapted cells go through a nonstandard pathway of cellular respiration. Furthermore, HNO-adapted SCCs displayed increased ribosomal production and genomic instability typical of CSCs. Our results clearly support the idea that CSCs are created from HNO- adaptation.