Membrane and cytoplasmic marker exchange between malignant neoplastic cells and fibroblasts via intermittent contact: increased tumour cell diversity independent of genetic change

2012 ◽  
Vol 228 (4) ◽  
pp. 495-505 ◽  
Author(s):  
Manu S David ◽  
Minh D Huynh ◽  
Elizabeth Kelly ◽  
Helen Rizos ◽  
Hedley Coleman ◽  
...  

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Michela Levi ◽  
Roberta Salaroli ◽  
Federico Parenti ◽  
Raffaella De Maria ◽  
Augusta Zannoni ◽  
...  

Abstract Background Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC). Results Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis. Conclusions DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.





2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i11-i12
Author(s):  
Andrew Donson ◽  
Kent Riemondy ◽  
Sujatha Venkataraman ◽  
Nicholas Willard ◽  
Anandani Nellan ◽  
...  

Abstract Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune cells contribute to disease progression. To better understand cellular heterogeneity in MB we used single-cell RNA sequencing, immunohistochemistry and deconvolution of transcriptomic data to profile neoplastic and immune populations in childhood MB samples and MB genetically engineered mouse models (GEMM). Neoplastic cells clustered primarily according to individual sample of origin which is in part due to the effect of chromosomal copy number gains and losses. Harmony alignment of single cell transcriptomic data revealed novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes and are associated with clinical outcomes. This includes photoreceptor-like cells and glutamatergic lineage unipolar brush cells in both GP3 and GP4 subgroups of MB, and a SHH subgroup nodule-associated neuronally-differentiated cell subpopulation. We definitively chart the spectrum of MB immune cell infiltrates, which reveals unexpected degree of myeloid cell diversity. Myeloid subpopulations include subgroup/subtype-associated developmentally-related neuron-pruning as well as antigen presenting myeloid cells. Human MB cellular diversity is recapitulated in subgroup-specific MB GEMM, supporting the fidelity of these models. These findings provide a clearer understanding of both the neoplastic and immune cell heterogeneity in MB and how these impact subgroup/subtype classification and clinical outcome.



The Lancet ◽  
1983 ◽  
Vol 321 (8318) ◽  
pp. 222
Keyword(s):  


Author(s):  
Thomas T.F. Huang ◽  
Patricia G. Calarco

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.



1952 ◽  
Vol 22 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Henry M. Lemon ◽  
Walter W. Byrnes


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
P Taylor ◽  
M Arsenak ◽  
MJ Abad ◽  
Á Fernández ◽  
R Gonto ◽  
...  


Planta Medica ◽  
2013 ◽  
Vol 79 (13) ◽  
Author(s):  
O Estrada ◽  
L González ◽  
M Mijares ◽  
Á Fernández ◽  
M Ruiz ◽  
...  


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