scholarly journals Evidence for the Participation of Interleukin-2 (IL-2) and IL-4 in the Regulation of Autonomous Growth and Tumorigenesis of Transformed Cells of Lymphoid Origin

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 610-620 ◽  
Author(s):  
Mona R. Hassuneh ◽  
Prakash S. Nagarkatti ◽  
Mitzi Nagarkatti

Abstract In the current study, we investigated the role of interleukin-2 (IL-2) and IL-4 as autocrine growth factors responsible for autonomous growth of four murine tumor cell lines: LSA, a radiation leukemia virus-induced T-cell lymphoma; EL-4, a chemically triggered T-cell lymphoma; PE-3T, a T-cell line that underwent spontaneous transformation ex vivo; and P815, a mastocytoma. All tumor cell lines screened constitutively expressed IL-2 receptor (IL-2R) and IL-4R genes. However, only LSA and PE-3T cells expressed IL-2 and IL-4 genes constitutively, whereas EL-4 and P815 tumor cells expressed only IL-4 but not IL-2. Monoclonal antibodies (MoAbs) against IL-2, IL-4, or a combination of these, as well as MoAbs against IL-2R significantly inhibited the proliferation of LSA but not that of other tumor cell lines ex vivo. To exclude the possibility that, in other tumor cell lines, the autocrine growth factor may interact with its receptor within the cell, the ability of antisense phosphorothioate oligonucleotides to inhibit the growth of the tumor cells was tested. The antisense phosphorothioate oligonucleotides specific for IL-2, IL-4, IL-2Rβ, or IL-2Rγ chains, added in culture, could markedly inhibit the growth of LSA but not that of the other tumor cell lines screened. Inasmuch as IL-2Rβ and IL-2Rγ subunits also serve as a component of the receptors for IL-4, IL-7, IL-9, and IL-15, the above data suggested that such cytokine redundancy was not responsible for autonomous growth of the other tumor cell lines. Addition of exogenous IL-2 or IL-4 to the tumor cell cultures caused significant enhancement in the proliferation of PE-3T cells, whereas other cell lines were either not significantly affected or slightly inhibited from growing. Interestingly, the LSA tumor growth in nude mice was significantly inhibited after treatment of these mice with a combination of MoAbs against IL-2 and IL-4. Together, our studies show for the first time that IL-2 and IL-4 may serve as autocrine growth factors in the autonomous proliferation of tumor cells, particularly those that are retrovirally induced. Second, some tumor cell lines, despite expressing certain cytokines and their receptors constitutively, may not depend exclusively on such factors for autocrine growth.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3391-3391
Author(s):  
Volker Kunzmann ◽  
Judith Engert ◽  
Brigitte Kimmel ◽  
Martin Wilhelm ◽  
Hermann Einsele

Abstract Activated Vγ9Vδ2 T cells, the major γδ T lymphocyte subset in humans, show cytolytic activity against various tumor cells. However, tumor antigens recognized by the TCR remained unkown so far. Recently, the ectopic surface expression of the F1-ATPase, normally expressed on the internal membrane of mitochondria, was implicated in tumor recognition of Vγ9Vδ2 T cells (Scotet E. et al., Immunity2005; 22:71–80). Surface expression of the a chain of the F1-ATPase (recognized by monoclonal antibody 7H10) strongly correlates with susceptibility of tumor cells against Vγ9Vδ2 T cell lysis. Different functions have been attributed to the ectopic expression of the F1-ATPase on the cell surface, including an immunoregulatory role induced by cell stress, receptor for angiostatin or regulation of lipoprotein transport through high-affinity apolipoprotein A-I binding. In this study we evaluated the surface expression of this F1-ATPase on hematopoetic tumor cell lines and on primary tumor cells from hematological malignancies. As already shown, the a subunit of F1-ATPase was clearly detected on several tumor cell lines which are consistently killed by activated Vγ9Vδ2 T cells (Daudi, K562, RPMI 8226), whereas the known Vγ9Vδ2 T cell resistant tumor cell lines (Raji, Jurkat) did not express detectable levels of the F1-ATPase. Analysis of 42 primary hematopoetic tumor cells (21 myeloma, 17 AML, 4 B-NHL) revealed frequent expression of F1-ATPase on primary myeloma cells (14/19 positive), whereas primary AML blasts (3/17 positive) and primary NHL cells (1/4 positive) expressed the putative Vγ9Vδ2-TCR ligand F1-ATPase less frequently. To further evaluate the functional role of F1-ATPase expression in Vγ9Vδ2 T cell mediated recognition of myeloma cells, cytotoxicity assays were performed. The mAb against the a subunit of F1-ATPase significantly decreased in vitro lysis of myeloma cells lines and primary myeloma cells by activated Vγ9Vδ2 T cells. These results suggests Vγ9Vδ2 TCR-dependent interactions between myeloma cells and Vγ9Vδ2 T cells and indicate that multiple myeloma should be considered as a major target for γδ T-cell mediated immunotherapy.


Virology ◽  
2002 ◽  
Vol 294 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Christine Reiss ◽  
Gerald Niedobitek ◽  
Simon Hör ◽  
Renate Lisner ◽  
Ute Friedrich ◽  
...  

Author(s):  
Mebirouk Romeila ◽  
Naimi Dalila ◽  
Riani Meriem ◽  
Antonicelli Frank

Objective: Despite the progress in cancer research, current therapies are ineffective and cause many adverse effects. The discovery of new natural anti-tumor agents that can act on multiple mechanisms of growth and tumor invasion with minor side effects and which can be safe for patients. Therefore, we sought new natural products from an invertebrate organism belonging to the phylum of mollusks: a land snail, Helix aspersa. This study was aimed to evaluate the cytotoxic activity of two extracts prepared from Helix aspersa, on two cutaneous T cell lymphoma cell line (HUT-78 and SeAx). Their effect on MMP-9 expression was also tested.Methods: We prepared from the snail Helix aspersa: an aqueous (AE) and a hydroalcoholic extracts (HAE). We have evaluated the concentration of total proteins and total phenols in these extracts. The percentage of cell mortality was evaluated after incubating the cell lines with the two extracts at different concentrations, by using trypan blue exclusion method. Finally, the tumor cells expression of metalloproteinase MMP-9 was examined by zymography analysis.Results: We have found that 1 mg/ml of AE contains (4.53±0.48 mg) of total proteins and (2.44±0.11 mg) GAE g-1of phenols. 1 mg/ml of HAE contains (1.83±0.23 mg) of total proteins and (2.81±0.16 mg) GAE g-1 of phenols. On one hand, both extracts exerted a toxic effect on these tumor cells. Indeed, aqueous extract induced 44.09 % mortality in HUT-78 and 31.47 % mortality in SeAx tumor cell line with 50 µg/ml. While, the hydroalcoholic extract induced 29.90 % in HUT-78 and 25 % in SeAx. On the other hand, the result showed no changes of MMP-9 expression.Conclusion: Helix aspersa’s extracts had a toxic effect on cutaneous T cell lymphoma (CTCL), but did not inhibit the production of the protease by these two cell lines in culture.


1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.


1974 ◽  
Vol 53 (3) ◽  
pp. 661-674 ◽  
Author(s):  
R. Cailleau ◽  
R. Young ◽  
M. Olivé ◽  
W. J. Reeves

Summary During 1973, 4 new epithelial tumor cell lines were isolated from pleural effusions from breast cancer patients. We describe 3 of these lines: MDA-MB-134, with a mean chromosome number of 43; MDA-MB-175, with a mean chromosome number of 49; and MDA-MB-231, with a mean chromosome number between 65 and 69. We isolated the same cell type from 4 of 10 effusions from MDA-MB-134 and from 6 of 8 effusions from MDA-MB-175. We found that pleural effusions as a source of breast tumor cells to be cultured and studied in vitro have the following advantages: 1) large amounts of material and the possibility of obtaining sequential samples from the same patient; 2) high viability of tumor cells; 3) scarcity or absence of fibroblasts; and 4) the possibility of separating the tumor cells from other “contaminating” cell types by differences in their speed or degree of attachment to the flask. All lines from different patients differed, as seen grossly and microscopically. All lines from sequential pleural effusions from the same patient were apparently alike. No viruses or mycoplasmas were detected in any line.


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