Identification And Long-term Culture Of Human Retinoblastoma Cancer Stem-like Cells And Preliminary Study Of Cancer Stem Cell Surface Markers

Retinoblastoma (RB) is the most common malignant tumor of the retina in children. Chemoreduction using systemic chemotherapy combined with local therapy (photoablation, cryotherapy or thermotherapy) has become a mainstay of therapy for retinoblastoma, which has improved prognosis and preserved the eye of patients. Nonetheless, chemotherapeutic drug resistance is common in retinoblastoma, resulting in the increased incidences of unsuccessful treatments. Previous studies showed that P-glycoprotein and multidrug resistance proteins (MRP) may contribute to drug resistance. However, the mechanism for resistance and recurrence is still not clear and improved targeted therapies are essential for alleviating this devastating malignancy.In past years, one emerging hypothesis postulates that the development of drug-resistant tumors is sustained by a self-renewing subpopulation termed as putative cancer stem cells (CSCs). Current therapies target rapidly dividing cells that comprise the bulk of the tumor while failing to eradicate the CSCs which subsequently re-initiate the entire malignancy. It is likely that these residual CSCs are able to survive in a dormant state for many years after remission due to their marked resistant ability. Although not all types of cancers follow the CSC theory, it provides a possible cellular mechanism to account for the metastasis and chemoresistance of RB. CSCs have been identified in many solid tumors including brain, breast, pancreas, prostate, melanoma, colon and ovarian cancers. However, compared to other solid tumors, cancer stem cell research is impeded in this intraocular cancer because of the shortage of fresh samples and difficulty of isolation from varying RB lesions, a mixture of tumor cells with necrosis and calcification.Therefore, a proper in vitro model is required to study retinoblastoma cancer stem-like cells and to design future therapeutic approaches. Here, we report that a long-term culture of sphere-forming cells from human retinoblastoma was established; these cells maintain their cancer stem-like cell properties including the ability of self-renewal, proliferation, differentiation, tumorigenicity and chemoresistance. Moreover, the expression of cell surface markers, such as ABCG2 (ATP-binding cassette superfamily G member 2), CD 133, CD44, has been studied on these cultured cells. Further research on surface marker for identifying retinoblastoma cancer stem-like cells (RCSC) may be carried out on these results.