A possible autocrine role for interleukin-6 in two lymphoma cell lines

Yee, Cassian; Biondi, Andrea; Wang, X. H.; Iscove, N. N.; Sousa, Josane de Freitas; La, Aarden; Wong, Gordon G.; Clark, Steven C.; Messner, Hans A.; Minden, Mark D.

doi:10.1182/blood.v74.2.798.798

Cited by 133 publications

(24 citation statements)

References 16 publications

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“…A possible autocrine role for IL-6 was also reported in non-Hodgkins lymphomas, chronic lymphocytic leukemias and acute myeloid leukemias [79, IL-6 was also demonstrated to be an autocrine growth factor for EBV-transformed B cell lines [89] and expression of an exogenous IL-6 gene in these B cell lines conferred growth advantage and in vivo tumorigenicity [90]. However, it has been controversial whether all myeloma cells actually produce IL-6, because only some myeloma cell lines were found to produce IL-6 [76,91-931, and bone marrow-adherent cells (rather than bone marrow nonadherent cell populations [86][87][88].…”

Section: Il-6 Is a Growth Factor For Plasmacytoma/myelomamentioning

confidence: 99%

Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

Hirano

1991

The International Journal of Cell Cloning

113

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Interleukin 6 (IL-6) is a multifunctional cytokine regulating immune response acute phase reaction and hematopoiesis. IL-6 plays a critical role in B cell differentiation to plasma cells and is a potent growth factor for plasmacytoma and myeloma. Abnormal production of IL-6 has been suggested to be involved in polyclonal plasma cell abnormalities and plasma cell neoplasias. The deregulated expression of the IL-6 gene in transgenic mice resulted in the generation of malignant plasmacytoma. Based on these findings, it could be considered that continuous IL-6 gene expression plays an essential role in a multistep oncogenesis of plasma cell neoplasias. The role of IL-6 and its receptor in the generation of plasma cell neoplasias and the mechanisms of the IL-6 gene expression and IL-6 receptor-mediated signal transduction are described.

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Section: Il-6 Is a Growth Factor For Plasmacytoma/myelomamentioning

confidence: 99%

Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

Hirano

1991

The International Journal of Cell Cloning

113

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“…Further analysis revealed that this cell line produced IL-6 protein and showed a n autocrine pattern 0 1991 WILEY-LISS, INC of growth control by IL-6. Rearrangement of the IL-6 gene did not account for the expression of IL-6 as Southern blot analysis of the IL-6 gene revealed that the OCI-LY3 cell line had a germline configuration of the IL-6 gene (Yee et al, 1989).…”

mentioning

confidence: 97%

“…OCI-LY13.1, a T-cell line of class I, does not express the message for IL-6. In contrast, the class 111 B-cell line OCI-LY3 expresses abundant IL-6 message and biologically active protein (Yee et al, 1989). Both cell lines are maintained in 10% human plasma in Iscove's medium.…”

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confidence: 99%

Regulation of interleukin‐6 expression in the lymphoma cell line OCI‐LY3

Yee

Messner

Minden

1991

Journal Cellular Physiology

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Previously we described a cell line OCI-LY3 derived from a patient with non-Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter.

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“…At present, nothing is known about an autocrine stimulation by IL-6 in malignant BL cells but the finding that IL-6 mRNA was detected in one of two investigated BL preparations (Freeman et al, 1989) supports this assumption. In two lymphoma cell lines of T-or B-cell origin, other than BL, IL-6 could be detected as an autocrine growth factor (Yee et al, 1989).…”

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confidence: 98%

Absence of IL‐6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL‐6 receptors by Epstein‐Barr virus in vitro

et al. 1997

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Summary. Interleukin-6 (IL-6) is a cytokine which is necessary for the differentiation of activated B cells and growth of early haemopoietic progenitors. It is used for exvivo expansion of myeloid progenitors in the setting of highdose chemotherapy with autologous bone marrow transplantation (BMT). Expression of the IL-6 receptor (IL-6R) was examined in six fresh Burkitt's lymphoma (BL) cell preparations and 12 BL cell lines by reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Inducibility of IL-6R mRNA expression by EpsteinBarr virus (EBV) was studied by comparing two uninfected cell lines with the same cell lines infected by EBV. The phenotype of the BL cells lines was analysed by FCM and by proliferation assays in the presence of anti-IgM antibodies.None of the fresh BL cells expressed the IL-6 receptor. The BL cell lines expressed varying degrees of IL-6R mRNA and protein. In vitro infection of EBV-negative BL cell lines resulted in up-regulation of IL-6R mRNA. There was no proliferative response of the BL cell lines to IL-6, including the cells that expressed the receptor. Compared to uninfected BL cell lines, EBV-infected cell lines and lymphoblastoid cell lines (LCLs) showed a weaker or no response to anti-IgM antibodies, indicating a more mature phenotype of these cells. We conclude that the IL-6 receptor is not expressed in fresh childhood BLs, but only in BL cell lines. EBV infection in vitro leads to an up-regulation of IL-6R mRNA but not to increased proliferation. This makes growth stimulation of contaminating BL cells in the setting of autologous BMT unlikely.

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A possible autocrine role for interleukin-6 in two lymphoma cell lines

Cited by 133 publications

References 16 publications

Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

Regulation of interleukin‐6 expression in the lymphoma cell line OCI‐LY3

Absence of IL‐6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL‐6 receptors by Epstein‐Barr virus in vitro

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