Hypoxia-activated ligand HAL-1/13 is lupus autoantigen Ku80 and mediates lymphoid cell adhesion in vitro

2001 ◽  
Vol 280 (4) ◽  
pp. C897-C911 ◽  
Author(s):  
Eileen M. Lynch ◽  
Robert B. Moreland ◽  
Irene Ginis ◽  
Susan P. Perrine ◽  
Douglas V. Faller
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Lymphoid Cell ◽  
Ectopic Expression ◽  
Lymphoid Cells ◽  
Expression Cloning ◽  
Hypoxic Exposure ◽  
Tumor Cell Lines ◽  
Human Lymphoid Cell

Hypoxia is known to induce extravasation of lymphocytes and leukocytes during ischemic injury and increase the metastatic potential of malignant lymphoid cells. We have recently identified a new adhesion molecule, hypoxia-activated ligand-1/13 (HAL-1/13), that mediates the hypoxia-induced increases in lymphocyte and neutrophil adhesion to endothelium and hypoxia-mediated invasion of endothelial cell monolayers by tumor cells. In this report, we used expression cloning to identify this molecule as the lupus antigen and DNA-dependent protein kinase-associated nuclear protein, Ku80. The HAL-1/13-Ku80 antigen is present on the surface of leukemic and solid tumor cell lines, including T and B lymphomas, myeloid leukemias, neuroblastoma, rhabdomyosarcoma, and breast carcinoma cells. Transfection and ectopic expression of HAL-1/13-Ku80 on (murine) NIH/3T3 fibroblasts confers the ability of these normally nonadhesive cells to bind to a variety of human lymphoid cell lines. This adhesion can be specifically blocked by HAL-1/13 or Ku80-neutralizing antibodies. Loss of expression variants of these transfectants simultaneously lost their adhesive properties toward human lymphoid cells. Hypoxic exposure of tumor cell lines resulted in upregulation of HAL-1/13-Ku80 expression at the cell surface, mediated by redistribution of the antigen from the nucleus. These studies indicate that the HAL-1/13-Ku80 molecule may mediate, in part, the hypoxia-induced adhesion of lymphocytes, leukocytes, and tumor cells.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

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.

scholarly journals A Nuclear-Directed Ribonuclease Variant Targets Cancer Stem Cells and Inhibits Migration and Invasion of Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Tumor Cell Lines

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.

scholarly journals Breast Tumor Cell Lines From Pleural Effusions2

1974 ◽  
Vol 53 (3) ◽  
pp. 661-674 ◽  
Author(s):  
R. Cailleau ◽  
R. Young ◽  
M. Olivé ◽  
W. J. Reeves
Keyword(s):  
Chromosome Number ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Tumor ◽  
Tumor Cell Lines ◽  
Breast Cancer Patients ◽  
Pleural Effusions ◽  
Epithelial Tumor

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.

scholarly journals Molecular Targets Modulated by Fangchinoline in Tumor Cells and Preclinical Models

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2538 ◽  
Author(s):  
Myriam Mérarchi ◽  
Gautam Sethi ◽  
Lu Fan ◽  
Srishti Mishra ◽  
Frank Arfuso ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Treatment Options ◽  
Molecular Targets ◽  
Tumor Cell Lines ◽  
Preclinical Models ◽  
Anticancer Activities ◽  
Hallmarks Of Cancer ◽  
Tremendous Progress

Despite tremendous progress made during the last few decades in the treatment options for cancer, compounds isolated from Mother Nature remain the mainstay for therapy of various malignancies. Fangchinoline, initially isolated from the dried root of Stephaniae tetrandrine, has been found to exhibit diverse pharmacological effects including significant anticancer activities both in tumor cell lines and selected preclinical models. This alkaloid appears to act by modulating the activation of various important oncogenic molecules involved in tumorigenesis leading to a significant decrease in aberrant proliferation, survival and metastasis of tumor cells. This mini-review briefly describes the potential effects of fangchinoline on important hallmarks of cancer and highlights the molecular targets modulated by this alkaloid in various tumor cell lines and preclinical models.

scholarly journals Cytotoxicity of farnesyltransferase inhibitors in lymphoid cells mediated by MAPK pathway inhibition and Bim up-regulation

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4872-4881 ◽  
Author(s):  
Husheng Ding ◽  
Jennifer Hackbarth ◽  
Paula A. Schneider ◽  
Kevin L. Peterson ◽  
X. Wei Meng ◽  
...  
Keyword(s):  
Cell Lines ◽  
Lymphoid Cell ◽  
Mapk Pathway ◽  
Lymphoid Cells ◽  
Farnesyltransferase Inhibitors ◽  
Death Domain ◽  
Nucleotide Exchange ◽  
Human Lymphoid Cell ◽  
Induced Apoptosis ◽  
Lymphoid Cell Lines

Abstract The mechanism of cytotoxicity of farnesyltransferase inhibitors is incompletely understood and seems to vary depending on the cell type. To identify potential determinants of sensitivity or resistance for study in the accompanying clinical trial (Witzig et al, page 4882), we examined the mechanism of cytotoxicity of tipifarnib in human lymphoid cell lines. Based on initial experiments showing that Jurkat variants lacking Fas-associated death domain or procaspase-8 undergo tipifarnib-induced apoptosis, whereas cells lacking caspase-9 or overexpressing Bcl-2 do not, we examined changes in Bcl-2 family members. Tipifarnib caused dose-dependent up-regulation of Bim in lymphoid cell lines (Jurkat, Molt3, H9, DoHH2, and RL) that undergo tipifarnib-induced apoptosis but not in lines (SKW6.4 and Hs445) that resist tipifarnib-induced apoptosis. Further analysis demonstrated that increased Bim levels reflect inhibition of signaling from c-Raf to MEK1/2 and ERK1/2. Additional experiments showed that down-regulation of the Ras guanine nucleotide exchange factor RasGRP1 diminished tipifarnib sensitivity, suggesting that H-Ras or N-Ras is a critical farnesylation target upstream of c-Raf in lymphoid cells. These results not only trace a pathway through c-Raf to Bim that contributes to tipifarnib cytotoxicity in human lymphoid cells but also identify potential determinants of sensitivity to this agent.

scholarly journals THE RELATIONSHIP BETWEEN ß2-MICROGLOBULIN AND IMMUNOGLOBULIN IN CULTURED HUMAN LYMPHOID CELL LINES

1973 ◽  
Vol 137 (3) ◽  
pp. 838-843 ◽  
Author(s):  
T. H. Hütteroth ◽  
H. Cleve ◽  
S. D. Litwin ◽  
M. D. Poulik
Keyword(s):  
Cell Surface ◽  
Cell Lines ◽  
Specific Antibody ◽  
Lymphoid Cell ◽  
Lymphoid Cells ◽  
Human Lymphoid Cell ◽  
Membrane Antigens ◽  
The Relationship ◽  
Lymphoid Cell Lines

ß2-microglobulin was detected on the cell surface and in the medium of human lymphoid cells established in long-term culture. The secretion of ß2-microglobulin was relatively uniform when different cell lines were compared, whereas IgG production varied widely. κ- and µ-membrane antigens were modulated by specific antibody; ß2-microglobulin was not modulated. Anti-κ and anti-µ antisera had no effect on the expression of membrane ß2-microglobulin, nor had anti-ß2-microglobulin antiserum any effect on the expression of κ- and µ-membrane antigens.

Expression and secretion of VEGF in solid tumor cells is mediated by the mammalian target of rapamycin (mTOR)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14123-14123
Author(s):  
E. M. Lackner ◽  
M. T. Krauth ◽  
R. Kondo ◽  
L. Rebuzzi ◽  
K. Eigenberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cell Lines ◽  
Primary Tumor ◽  
Tumor Cell Lines ◽  
Neoplastic Cells ◽  
Malignant Effusions ◽  
Vegf Protein

14123 Background: Tumor progression and metastasis formation are often associated with enhanced angiogenesis and with the formation of malignant effusions. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and a mediator of vascular permeability. We here describe that VEGF is produced and secreted by neoplastic cells in various solid tumors and its production mediated through mTOR. Methods and Results: As assessed by ELISA, the VEGF protein was detected in supernatants of cell lines derived from breast cancer (MDA-MB231), pancreatic carcinoma (BxPC-3), lung cancer (A-427), colon carcinoma (HCT8), and cholangiocellular carcinoma (EGI-1). In addition, VEGF was detected in supernatants of primary tumor cells obtained from malignant effusions in various malignancies (breast cancer, n=4; pancreatic cancer, n=1; ovarial cancer, n=1; parotic carcinoma, n=1; oesophageal carcinoma, n=1). In each case, VEGF protein was detectable in neoplastic cells by immunocytochemistry, and was found to accumulate in supernatants of cultured tumor cells over time, suggesting constant production and secretion. Correspondingly, as assessed by RT-PCR, primary tumor cells as well as the cell lines tested were found to express VEGF mRNA in a constitutive manner. Since mTOR is a well known regulator of VEGF synthesis, we applied rapamycin on primary neoplastic cells and on tumor cell lines. Rapamycin (20–200 nM) was found to counteract the production and secretion of VEGF in all tumor cells tested (VEGF in supernatants in cultures supplemented with rapamycin at 100 nM compared to control=100% on day 6: MDA-MB231: 11.8±0.2%; BxPC-3: 23.6±18.8%; A-427: 30.1±3.4%; HCT8 17.2±0.5%; EGI-1 28.4±1.1%; p<0.05). By contrast, neither rapamycin nor VEGF were found to modulate growth of primary tumor cells or the growth of the tumor cell lines tested. Conclusions: Various human tumor cells express and secrete VEGF. VEGF production is mediated through mTOR. These observations may have implications for the design of new treatment approaches attempting to counteract VEGF production/secretion and thus VEGF-dependent angiogenesis and effusion- formation in solid tumors. No significant financial relationships to disclose.

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