scholarly journals Activation of platelet heparitinase by tumor cell-derived factors

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 789-796 ◽  
Author(s):  
A Haimovitz-Friedman ◽  
DJ Falcone ◽  
A Eldor ◽  
V Schirrmacher ◽  
I Vlodavsky ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mammalian Cells ◽  
Human Platelets ◽  
Native Form ◽  
Heat Stable ◽  
Inactive Form ◽  
Cell Lining ◽  
Mouse Lymphoma

Abstract The nature of the cooperation between platelets and tumor cells during the process of blood-borne metastasis is essentially unknown. In previous in vitro studies we showed that platelets participated in the formation of gaps in the endothelial cell lining, and that concomitantly heparan sulfate glycosaminoglycans were degraded by the platelet heparitinase, released on activation of platelets. In the current study we show that the ability to degrade proteoheparan sulfate derived from endothelial extracellular matrix is gradually eliminated when the number of human platelets is decreased from 5 x 10(7) to 10(6) cells/mL. When aliquots of conditioned media or lysates of either Eb or heat-inactivated ESb mouse lymphoma cells (both of which showed no heparanase activity) were added to freeze-thawed lysates of 10(6) platelets, a reappearance of platelet heparitinase activity was observed. A similar activation was not elicited by lysates of several normal mammalian cells. These data suggest that in its native form, a fraction of the platelet heparitinase is stored in an inactive form that can be activated by a factor secreted by lymphoma, but not by normal cells. Partial characterization of the heparitinase-activating factor showed that it is a heat-stable polyanionic molecule, devoid of proteolytic activity and resistant to both proteolytic and chondroitinase digestions. Activation of platelet heparitinase was also observed on coincubation with chondroitinases ABC and AC, suggesting that the inactive form of platelet heparitinase could result from a complex formation with a chondroitinase-sensitive proteoglycan. The lymphoma-derived heparitinase activating factor itself is, however, not a chondroitinase, because activity of chondroitinase could not be detected in Eb and ESb cells. A possible mechanism by which tumor cells recruit and regulate the activity of platelet heparitinase, and its relevance to the progression of blood borne metastasis, is discussed.

scholarly journals Activation of platelet heparitinase by tumor cell-derived factors

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 789-796
Author(s):  
A Haimovitz-Friedman ◽  
DJ Falcone ◽  
A Eldor ◽  
V Schirrmacher ◽  
I Vlodavsky ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mammalian Cells ◽  
Human Platelets ◽  
Native Form ◽  
Heat Stable ◽  
Inactive Form ◽  
Cell Lining ◽  
Mouse Lymphoma

The nature of the cooperation between platelets and tumor cells during the process of blood-borne metastasis is essentially unknown. In previous in vitro studies we showed that platelets participated in the formation of gaps in the endothelial cell lining, and that concomitantly heparan sulfate glycosaminoglycans were degraded by the platelet heparitinase, released on activation of platelets. In the current study we show that the ability to degrade proteoheparan sulfate derived from endothelial extracellular matrix is gradually eliminated when the number of human platelets is decreased from 5 x 10(7) to 10(6) cells/mL. When aliquots of conditioned media or lysates of either Eb or heat-inactivated ESb mouse lymphoma cells (both of which showed no heparanase activity) were added to freeze-thawed lysates of 10(6) platelets, a reappearance of platelet heparitinase activity was observed. A similar activation was not elicited by lysates of several normal mammalian cells. These data suggest that in its native form, a fraction of the platelet heparitinase is stored in an inactive form that can be activated by a factor secreted by lymphoma, but not by normal cells. Partial characterization of the heparitinase-activating factor showed that it is a heat-stable polyanionic molecule, devoid of proteolytic activity and resistant to both proteolytic and chondroitinase digestions. Activation of platelet heparitinase was also observed on coincubation with chondroitinases ABC and AC, suggesting that the inactive form of platelet heparitinase could result from a complex formation with a chondroitinase-sensitive proteoglycan. The lymphoma-derived heparitinase activating factor itself is, however, not a chondroitinase, because activity of chondroitinase could not be detected in Eb and ESb cells. A possible mechanism by which tumor cells recruit and regulate the activity of platelet heparitinase, and its relevance to the progression of blood borne metastasis, is discussed.

scholarly journals Characterization of a Cytotoxic Factor in Culture Filtrates of Serratia marcescens

2002 ◽  
Vol 70 (3) ◽  
pp. 1121-1128 ◽  
Author(s):  
Kent B. Marty ◽  
Christopher L. Williams ◽  
Linda J. Guynn ◽  
Michael J. Benedik ◽  
Steven R. Blanke
Keyword(s):  
Cytotoxic Activity ◽  
Serratia Marcescens ◽  
Mammalian Cells ◽  
Divalent Cations ◽  
Recombinant Expression ◽  
Cytotoxic Factor ◽  
Culture Filtrates ◽  
Type Strains

ABSTRACT Serratia marcescens culture filtrates have been reported to be cytotoxic to mammalian cells. Using biochemical and genetic approaches, we have identified a major source of this cytotoxic activity. Both heat and protease treatments abrogated the cytotoxicity of S. marcescens culture filtrates towards HeLa cells, suggesting the involvement of one or more protein factors. A screen for in vitro cytotoxic activity revealed that S. marcescens mutant strains that are deficient in production of a 56-kDa metalloprotease are significantly less cytotoxic to mammalian cells. Cytotoxicity was significantly reduced when culture filtrates prepared from wild-type strains were pretreated with either EDTA or 1,10-phenanthroline, which are potent inhibitors of the 56-kDa metalloprotease. Furthermore, cytotoxic activity was restored when the same culture filtrates were incubated with zinc divalent cations, which are essential for enzymatic activity of the 56-kDa metalloprotease. Finally, recombinant expression of the S. marcescens 56-kDa metalloprotease conferred a cytotoxic phenotype on the culture filtrates of a nonpathogenic Escherichia coli strain. Collectively, these data suggest that the 56-kDa metalloprotease contributes significantly to the in vitro cytotoxic activity commonly observed in S. marcescens culture filtrates.

scholarly journals B-1 cell: the precursor of a novel mononuclear phagocyte with immuno-regulatory properties

2009 ◽  
Vol 81 (3) ◽  
pp. 489-496 ◽  
Author(s):  
José Daniel Lopes ◽  
Mario Mariano
Keyword(s):  
Mammalian Cells ◽  
Giant Cells ◽  
Mononuclear Phagocyte ◽  
Different Types ◽  
Series Of Experiments ◽  
B1 Cells ◽  
Regulatory Properties

Characterization of the origin, properties, functions and fate of cells is a fundamental task for the understanding of physiological and pathological phenomena. Despite the bulk of knowledge concerning the diverse characteristics of mammalian cells, some of them, such as B-1 cells, are still poorly understood. Here we report the results obtained in our laboratory on these cells in the last 10 years. After showing that B-1 cells could be cultured and amplified in vitro, a series of experiments were performed with these cells. They showed that B1 cells reside mostly in the peritoneal and pleural cavities, migrate to distant inflammatory foci, coalesce to form giant cells and participate in granuloma formation, both in vitro and in vivo. They are also able to present antigens to immunologically responsive cells and are endowed with regulatory properties. Further, we have also shown that these cells facilitate different types of infection as well as tumor growth and spreading. These data are presently reviewed pointing to a pivotal role that these cells may play in innate and acquired immunity.

scholarly journals Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells

2020 ◽  
Vol 9 (2) ◽  
pp. 353 ◽  
Author(s):  
Manuel Abreu ◽  
Pablo Cabezas-Sainz ◽  
Thais Pereira-Veiga ◽  
Catalina Falo ◽  
Alicia Abalo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mesenchymal Transition ◽  
Intermediate Phenotypes ◽  
Tumor Dissemination

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients’ outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer.

In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex

2016 ◽  
Vol 12 (3) ◽  
pp. 1015-1023 ◽  
Author(s):  
Marta Martins ◽  
Pedro V. Baptista ◽  
Ana Soraia Mendo ◽  
Claudia Correia ◽  
Paula Videira ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Proliferative Potential ◽  
Biological Characterization ◽  
Growth Of Tumor

Identification of novel molecules that can selectively inhibit the growth of tumor cells, is of utmost importance.

scholarly journals In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

2006 ◽  
Vol 17 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Daniel Araki Ribeiro ◽  
Mariângela Esther Alencar Marques ◽  
Daisy Maria Fávero Salvador
Keyword(s):  
Comet Assay ◽  
Single Cell ◽  
Mammalian Cells ◽  
Lymphoma Cells ◽  
Trypan Blue Exclusion ◽  
Trypan Blue Exclusion Test ◽  
Gutta Percha ◽  
Mouse Lymphoma Cells ◽  
Mouse Lymphoma

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 muL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Sign in / Sign up

Export Citation Format

Share Document