177: The “Side-Population” in Human Lymphoma Cell Lines have Increased Chemo-Resistance, Stem-Like Properties, as a Target for Immunotherapy
Year: 2008
Type: article
Abstract: We previously demonstrated that cancer cells contain a distinct “side-population” (SP), characterized by active transport of Hoechst fluorescent dye. The mechanisms responsible for Hoechst efflux also contribute to resistance to chemotherapy. This population has been shown to be enriched for tumor initiating cells in several human cancer models. We hypothesize that targeting the cancer “SP” cells using immunotherapy will eliminate the cell population least sensitive to chemotherapy and enriched for tumor repopulating potential which may prevent relapse. In this study we characterize SP cells in ten Human Lymphoma Cell Lines. We show that that 5 of the 10 lymphoma cell lines tested (HDLM2, L428, Ramos, Toledo, Karpas) had a distinct SP ranging from 0.8–2%. In vitro these SP cells can repopulate both the SP and non-SP cells. Gene expression analysis of the SP showed increased expression of ABCG2 and other ABC transporters that mediate both the transport of Hoechst dye and other drugs including some chemotherapeutic agents out of the cell. Further, we demonstrated that cell lines with a SP are resistant to the chemotherapeutic drug gemcitabine, and within these lines it the SP cells that are preferentially resistant to this agent. The cell lines that did not have SP showed either complete or partial sensitivity to this drug. In addition, we demonstrated that the SP population is enriched for the cancer testis antigen's MAGE-4, SSX2 and NY-ESO. These antigens are attractive targets for cytotoxic T lymphocyte therapy since: they are immunogenic, have restricted expression in normal tissues, and are expressed in many cancers. These tumor antigens may render SP cells susceptible to T cell mediated destruction indicating that T cell therapy may have a powerful effect on drug resistant tumor cells when used as adjunct therapy.
Institution: Baylor College of Medicine
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2076381817