title: Resistance to cytotoxic chemotherapy is induced by NK cells in non-Hodgkin's Lymphoma Cells.
abstract: It is known that B lymphoma cells are sensitive to cytotoxic chemotherapy, but primary or secondary chemoresistance frequently occurs and is the major cause of death in these patients. However, the mechanisms by which lymphoma cells acquire resistance to cytotoxic drugs are not fully understood. Recently, it was reported that B cells secrete immunoglobulin and produce cytokines after interacting with NK cells, thus indicating the importance of NK/B interactions. In this study, we investigated the mechanism of resistance to cytotoxic chemotherapy induced in cocultures of NK cells and Raji cells. Normally, Raji cells are doxorubicin-sensitive, but Raji cells cocultured with NK cells become doxorubicin-resistant. In addition, we detected the upregulation of CD69 and CD70 on Raji cells cocultured with NK cells, suggesting that Raji cells are activated by NK cells. We also found that the resistance of Raji cells to doxorubicin increased when they had been treated with NK cell coculture supernatant. Furthermore, boiled culture supernatant did not inhibit doxorubicin-mediated cell death, indicating that soluble factors are involved. Finally, we confirmed that NK cells produce TNF alpha, and that doxorubicin-sensitive Raji cells become doxorubicin-resistant after TNF alpha treatment. Taken together, these results suggest that B lymphoma cell resistance to doxorubicin-mediated cell death is induced by coculture with NK cells, because of TNF alpha secretion.
authors.affiliation: Department of Life Science, Sookmyung Women's University.
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kim
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Eunsil
authors.initials: E
authors.lastname: Hahm
authors.forename: Yoolhee
authors.initials: Y
authors.lastname: Yang
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Seonghan
authors.initials: S
authors.lastname: Kim
authors.forename: Yeong Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Hur
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Park
authors.forename: Young Il
authors.initials: YI
authors.lastname: Hwang
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018920:Coculture Techniques; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin