TLR4 and MyD88 Expression in Cancer Stem Cells.
Aoife A Cooke, Michael F Gallagher, Sharon A O'Toole, Cara M Martin, Orla M Sheils, John J O'Leary. University of Dublin, Trinity College, College Green, Ireland
Background: Ovarian cancer is the most common cause of gynaecologic cancer death in the western world. Although most patients respond positively to initial therapy, a high proportion of patients will face the development of chemoreistant recurrent disease over their lifetime. One suggested mechanism for this is the cancer stem cell theory. Cancer stem cells (CSCs) are a minority population of cancer cells which display stem like characteristics including enhanced proliferation. They are also known to display chemoresistance.
Design: Cell line experiments were carried out in two CSC lines: NTera2 and 2102Ep. NTera2 cells are pluripotent and readily differentiate in response to retinoic acid treatment while 2102Ep cells are nullipotent and resist differentiation via retinoic acid. Cells were incubated in the presence of both retinoic acid and cisplatin. RNA was isolated from treated cells and interrogated for mRNA expression via Q-PCR.
Results: Both NTera2 and 2102Ep cells showed alterations in the TLR4/MyD88 pathway following treatment with retinoic acid. Following on from this it was decided to treat both cell lines with cisplatin and assay for a possible TLR4 response. Both cell lines showed an alteration in TLR4 signalling, however in opposite directions. Given the difference in chemosensitivity between the two cell lines we hypothesise that this difference is important in chemoreistance of these cells. Experiments involving predifferentiation of cells via retinoic acid followed by cisplatin treatment were also performed. We are currently performing functional analysis on the TLR4 pathway to clarify its potential role in chemoresistance.
Conclusions: Our results show for the first time that TLR4 and MyD88 are involved in the cellular response to both differentiation and cisplatin treatment. The difference in response between the two cells when viewed with the differing chemosensitivies of the two lines suggest that this difference may be involved in their levels of chemoresistance. The TLR4/MyD88 mechanism was also found to be linked with differentiation, chemoresistance and differentiation avoidance. We are currently performing further experiments to investigate this. Acknowledgments Funded by Cancer Research Ireland
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Monday, February 28, 2011 1:00 PM
Poster Session II # 238, Monday Afternoon