Chemo-resistant cells contain cancer stem like cells

Abstract

One of the hypotheses in cancer stem cell biology is that chemotherapy kills most cancer cells but leave cancer stem cells behind. It is generally accepted that high expression level of specific ABC drug transporters in cancer stem cells contribute to drug resistance. However, purified ABCG2+ cancer cells have very similar or less tumorigenicity to the ABCG2- cells; and whether ABCG2+ or ABCG2- represents more caner stem like cells is yet conclusive. We used anticancer drugs such as doxorubicin, 5-FU, and cisplatin either alone or with combination to treat several cancer cell lines. Using RT-PCR, cell migration, colony forming and Xenograft tumorgenesis assay, we observed cell markers, biological features and xenograft tumorigenesis in those chemo resistant cells. Chemo-resistant Hela and liver cancer cells showed enhanced expression of stem cell like markers Oct4 and ABCG2, as well as liver progenitor cell markers CK19 and CC-6. Epithelial mesenchymal transition (EMT) related molecular markers such as N-cadherin and Notch1-Snail pathway were also increased. Chemo-resistant cancer cells displayed increased cell migration and potential metastatic tendency in Xenograft tumor. We also found that self-renewal ability of chemo-resistant cancer cells had enhanced self-renewal ability by colony forming assay in 0.5% serum containing medium but not in 1% serum containing medium. The present study demonstrated that chemo-resistant cells might have stem cell potential and their enhanced migration might contribute to tumor metastasis and recurrence.