Effect of tubulin-binding agents on the infiltration of tumour cells into primary hepatocyte cultures

1982 ◽  
Vol 55 (1) ◽  
pp. 233-245
Author(s):  
E. Roos ◽  
de Pavert IV Van
Keyword(s):  
Cell Types ◽  
Carcinoma Cells ◽  
Morphological Evidence ◽  
Rat Hepatocyte ◽  
Hepatocyte Cultures ◽  
Tubulin Binding ◽  
Binding Agents ◽  
Primary Hepatocyte Cultures ◽  
Mammary Carcinoma Cells ◽  
Dependent Processes

The influence of tubulin-binding agents on the infiltration of murine MB6A lymphosarcoma and TA3 mammary carcinoma cells into primary rat hepatocyte cultures was studied. Colchicine, nocodazole and vinblastine reduced the number of infiltrating lymphosarcoma cells, probably by interfering with the adhesion of these cells to the exposed hepatocyte surface. However, the subsequent infiltration of cells that did adhere was not affected or even slightly stimulated. The reduced adhesion appears to be due to an effect on both the MB6A cells and the hepatocytes. In contrasts, adhesion of TA3 cells was not reduced and infiltration was markedly enhanced by these agents, due to an effect on the TA3 cells but probably not on the hepatocytes. These observations support previously described morphological evidence for differences between the infiltration mechanisms of the two tumour cell types. It is concluded that the system within the hepatocytes involved in adhesiveness of the exposed surface to MB6A cells is distinct from that mediating other types of adhesion. The tendency of TA3 cells to invaginate hepatocytes may be due to disturbances in tubulin-dependent processes.

Infiltration of tumour cells into cultures of isolated hepatocytes

1981 ◽  
Vol 47 (1) ◽  
pp. 385-397 ◽  
Author(s):  
E. Roos ◽  
I.V. Van de Pavert ◽  
O.P. Middelkoop
Keyword(s):  
Tumour Cell ◽  
Liver Parenchyma ◽  
Cell Types ◽  
Isolated Hepatocytes ◽  
Liver Cells ◽  
Bile Canaliculus ◽  
Tumour Cells ◽  
Carcinoma Cells ◽  
Suitable Model ◽  
Mammary Carcinoma Cells

MB 6A lymphosarcoma and TA3 mammary carcinoma cells have previously been shown to infiltrate from liver blood vessels, where they had been arrested, into the liver parenchyma. The same tumour cells were previously added to cultures of isolated hepatocytes, 24 h after their isolation. Both tumour cell types adhered to both dorsal and lateral surfaces of hepatocytes. The lymphosarcoma cells rapidly infiltrated between the hepatocytes. They first extended pointed pseudopods between the liver cells, and when the tumour cell body intruded, they deeply invaginated the liver cells at an interhepatocyte boundary. The MB A6 cells accumulated between and under the hepatocytes, and after 24 h virtually all cells were contained within the cultures. TA3 cells also invaginated hepatocytes, not only at interhepatocyte boundaries, but all over the exposed surface. They did not extent pseudopods. The process was much slower than with MB 6A cells: After 24 h a few TA3 cells were completely encircled by hepatocytes. These observations indicate that the mechanism of infiltration is different from the 2 tumour cell types. Part of the TA3 cell did not invaginate the hepatocytes. Several of these cells spread on th hepatocyte surface, attaining a flattened shape. TA3 cells formed extensive tight junctions with the hepatocytes, sometimes sealing an intercellular lumen that resembled both a tumour acinus and a bile canaliculus. Also desmosomes were occasionally formed. The hepatocyte cultures appear to be a suitable model for studying the mechanism of liver infiltration, not only of tumour cells, but also leucocytes.

scholarly journals Metabolomic Profile of Primary Turkey and Rat Hepatocytes and Two Cell Lines after Chloramphenicol Exposure

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Lidia Radko ◽  
Tomasz Śniegocki ◽  
Bartosz Sell ◽  
Andrzej Posyniak
Keyword(s):  
Cell Lines ◽  
Membrane Integrity ◽  
Rat Hepatocytes ◽  
Cellular Membrane ◽  
Primary Hepatocyte ◽  
Rat Hepatocyte ◽  
Hepatocyte Cultures ◽  
3T3 Fibroblasts ◽  
Primary Hepatocyte Cultures ◽  
Toxicity Of Drugs

The purpose of this study was to assess the formation of chloramphenicol metabolites in primary turkey and rat hepatocyte cultures and human hepatoma (HepG2) cells and nonhepatic, Balb/c 3T3 fibroblasts. Additionally, the cytotoxicity of the drug was assessed through three biochemical endpoints: mitochondrial and lysosomal activity and cellular membrane integrity after 24 and 48 h exposure. The two metabolites of the drug, chloramphenicol glucuronide and nitroso-chloramphenicol, were detected to the greatest extent in both primary hepatocyte cultures by liquid chromatography–tandem mass spectrometry. Toxic nitroso-chloramphenicol was the main metabolite in the primary turkey hepatocyte cultures, but it was not in the primary rat hepatocyte cultures. The most affected endpoint in turkey and rat hepatocyte cultures was the disintegration of the cellular membrane, but in the cell lines, mitochondrial and lysosomal activities underwent the greatest change. The primary hepatocyte cultures represent valuable tools with which to study the species differences in the biotransformation and toxicity of drugs. To the best of our knowledge, this is the first report of differences in chloramphenicol metabolism in primary turkey and rat hepatocyte cultures.

Ultrastructural Study of a differentiating human colon carcinoma cell line

1990 ◽  
Vol 48 (3) ◽  
pp. 208-209
Author(s):  
Sylvie Polak-Charcon ◽  
Mehrdad Hekmati ◽  
Yehuda Ben Shaul
Keyword(s):  
Cell Line ◽  
Morphological Changes ◽  
Secretory Granules ◽  
Human Colon ◽  
Cell Types ◽  
Culture Conditions ◽  
Morphological Evidence ◽  
Human Colon Carcinoma Cell ◽  
Colon Cell

The epithelium of normal human colon mucosa “in vivo” exhibits a gradual pattern of differentiation as undifferentiated stem cells from the base of the crypt of “lieberkuhn” rapidly divide, differentiate and migrate toward the free surface. The major differentiated cell type of the intestine observed are: absorptive cells displaying brush border, goblet cells containing mucous granules, Paneth and endocrine cells containing dense secretory granules. These different cell types are also found in the intestine of the 13-14 week old embryo.We present here morphological evidence showing that HT29, an adenocarcinoma of the human colon cell line, can differentiate into various cell types by changing the growth and culture conditions and mimic morphological changes found during development of the intestine in the human embryo.HT29 cells grown in tissue-culture dishes in DMEM and 10% FCS form at late confluence a multilayer of morphologically undifferentiated cell culture covered with irregular microvilli, and devoid of tight junctions (Figs 1-3).

Toxicological properties of thymoquinone in primary rat hepatocyte cultures

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
M Khader ◽  
N Bresgen ◽  
P Eckl
Keyword(s):  
Rat Hepatocyte ◽  
Hepatocyte Cultures

scholarly journals THE EXTRACELLULAR MATRIX CONTROL OF ACUTE PHASE RESPONSE IN RAT HEPATOCYTE CULTURES

Shock ◽  
1995 ◽  
Vol 4 (Supplement) ◽  
pp. 52
Author(s):  
E. Adoeva ◽  
T. Stepanova ◽  
I. Diakonov ◽  
A. Polevschlkov
Keyword(s):  
Extracellular Matrix ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Rat Hepatocyte ◽  
Hepatocyte Cultures ◽  
Matrix Control

735 Impact of reversing an epithelial-to-mesenchymal transition program on tumor metabolism and immune suppression

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A779-A779
Author(s):  
Michelle Williams ◽  
Jessica Christenson ◽  
Kathleen O’Neill ◽  
Sabrina Hafeez ◽  
Nicole Spoelstra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Survival ◽  
Conditioned Medium ◽  
Mammary Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Macrophage Polarization ◽  
Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Raw264.7 Macrophages ◽  
Mammary Carcinoma Cells

BackgroundTo identify novel molecular mechanisms used by triple negative breast cancer (TNBC) to facilitate metastasis, we manipulated oncogenic epithelial-to-mesenchymal transition (EMT) by restoring the microRNA-200c (miR-200c), termed ‘the guardian of the epithelial phenotype.’ We identified several tumor cell catabolizing enzymes, including tryptophan 2,3-dioxygenase (TDO2) and heme oxygenase-1 (HO-1). The Richer lab has published that TDO2 promotes anchorage independent cell survival during TNBC metastasis via its catabolite kynurenine, which also induces CD8+ T cell death. Similarly, published studies have demonstrated that HO-1 supports BC anchorage independent survival. However, effects of the HO-1 catabolite bilirubin on the tumor microenvironment had not been studied. We postulated that TNBC utilize targetable catabolizing enzymes, like HO-1, to simultaneously support tumor cell survival and dampen the anti-tumor immune response.MethodsTo test our hypothesis in an immune competent mouse model, Met-1 mammary carcinoma cells from a late stage MMTV-PyMT tumor were engineered to inducibly express miR-200c. Tumor cell infiltrates were analyzed by immunohistochemistry (IHC), flow cytometry and multispectral fluorescence. RAW264.7 mouse macrophages were cultured with conditioned medium from carcinoma cells ± miR-200c or the HO-1 competitive inhibitor tin mesoporphyrin (SnMP). RAW264.7 macrophages were also treated with 0–20 µM bilirubin and macrophage polarization and efferocytic capacity, the ability to engulf dead tumor cells, were assessed using qRT-PCR and IncuCyte assays.ResultsMiR-200c restoration to Met-1 orthotopic tumors decreased growth by 45% and increased infiltration of CD11c+ dendritic cells and activation, determined by CD44 expression, of CD4+ and CD8+ T cells. While the number of F4/80+ macrophages was unchanged by miR-200c, the percent of M1 anti-tumor macrophages (F4/80+iNOS+/total cells) increased by >6-fold in miR-200c+tumors. RAW264.7 macrophages cultured with conditioned medium from miR-200c-restored mammary carcinoma cells had a 25–95% decrease in M2 pro-tumor genes (Arg1, Il4 and Il13) and a 15–55% increase in M1 genes (Nos2, Tnfa and Cxcl10). A similar decrease in M2 (30–50%) and increase M1 (35–160%) genes was seen in macrophages cultured with conditioned medium from SnMP treated mammary carcinoma cells. Conversely, bilirubin treatment alone enhanced M2 macrophage polarization and inhibited efferocytosis in a dose-dependent manner.ConclusionsUse of miR-200c to reverse EMT revealed that HO-1 promotes simultaneous TNBC cell survival and immune suppression. These studies are the first to show that tumor cell-HO-1 activity and subsequent bilirubin production may alter macrophage function in the tumor microenvironment. This finding could be clinically relevant since HO-1 inhibitors like SnMP are already FDA approved for treatment of other diseases.

Syndecan-1 regulates FGF8b responses in S115 mammary carcinoma cells

2006 ◽  
Vol 24 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Leif Viklund ◽  
Natalia Vorontsova ◽  
Tiina Henttinen ◽  
Markku Salmivirta
Keyword(s):  
Mammary Carcinoma ◽  
Carcinoma Cells ◽  
Mammary Carcinoma Cells
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