scholarly journals Cancer cell exosomes can initiate malignant cell transformation

2018 ◽  
Author(s):  
Karoliina Stefanius ◽  
Kelly A. Servage ◽  
Marcela de Souza Santos ◽  
Jason Toombs ◽  
Hillery Fields Gray ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Tumor Formation ◽  
Transformed Cells ◽  
Proteomic Profiling ◽  
Genetic Changes ◽  
Pancreatic Cancer Cells ◽  
Multistep Process ◽  
Malignant Cell Transformation

AbstractCancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations mediated by intracellular and extracellular cues. We observe that exosomes isolated from pancreatic cancer cells, but not normal pancreatic cells, can initiate the first step of malignant cell transformation. Injection of exosome-initiated transformed cells into mice results in aggressive tumor growth. Using proteomic profiling and DNA sequencing of exosome-treated and transformed cells, we show that cancer cell exosomes act as a classic initiator by causing random genetic changes in recipient cells. Our studies provide new insight into a function of cancer cell exosomes and how they might specifically contribute to orchestrated local cell transformation.One Sentence SummaryExosomes function as aninitiatorof tumor formation.

scholarly journals Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Karoliina Stefanius ◽  
Kelly Servage ◽  
Marcela de Souza Santos ◽  
Hillery Fields Gray ◽  
Jason E Toombs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cell ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Human Pancreatic Cancer ◽  
Editorial Note ◽  
Genetic Profile ◽  
Pancreatic Cancer Cells ◽  
Multistep Process

Cancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations. Tumor-derived exosomes are emerging contributors to tumorigenesis. To understand how exosomes might contribute to cell transformation, we utilized the classic two-step NIH/3T3 cell transformation assay and observed that exosomes isolated from pancreatic cancer cells, but not normal human cells, can initiate malignant cell transformation and these transformed cells formed tumors in vivo. However, cancer cell exosomes are unable to transform cells alone or to act as a promoter of cell transformation. Utilizing proteomics and exome sequencing, we discovered cancer cell exosomes act as an initiator by inducing random mutations in recipient cells. Cells from the pool of randomly mutated cells are driven to transformation by a classic promoter resulting in foci, each of which encode a unique genetic profile. Our studies describe a novel molecular understanding of how cancer cell exosomes contribute to cell transformation.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that major issues remain unresolved (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals The Role of the MCTS1 and DENR Proteins in Regulating the Mechanisms Associated with Malignant Cell Transformation

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 98-105
Author(s):  
Elena Yu. Shyrokova ◽  
Vladimir S. Prassolov ◽  
Pavel V. Spirin
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Tumor Formation ◽  
Anti Cancer ◽  
Differentiation And Proliferation ◽  
Mutant Genes ◽  
Malignant Cell Transformation

The mutations associated with malignant cell transformation are believed to disrupt the expression of a significant number of normal, non-mutant genes. The proteins encoded by these genes are involved in the regulation of many signaling pathways that are responsible for differentiation and proliferation, as well as sensitivity to apoptotic signals, growth factors, and cytokines. Abnormalities in the balance of signaling pathways can lead to the transformation of a normal cell, which results in tumor formation. Detection of the target genes and the proteins they encode and that are involved in the malignant transformation is one of the major evolutions in anti-cancer biomedicine. Currently, there is an accumulation of data that shed light on the role of the MCTS1 and DENR proteins in oncogenesis.

scholarly journals Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme

2020 ◽  
Vol 94 (11) ◽  
pp. 3911-3927 ◽  
Author(s):  
Tina Kostka ◽  
Jörg Fohrer ◽  
Claudia Guigas ◽  
Karlis Briviba ◽  
Nina Seiwert ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Malignant Cell ◽  
Red Meat ◽  
Colorectal Carcinogenesis ◽  
In Vivo Studies ◽  
Processed Meat ◽  
Cell Transforming ◽  
Malignant Cell Transformation

Abstract Data from epidemiological studies suggest that consumption of red and processed meat is a factor contributing to colorectal carcinogenesis. Red meat contains high amounts of heme, which in turn can be converted to its nitrosylated form, NO-heme, when adding nitrite-containing curing salt to meat. NO-heme might contribute to colorectal cancer formation by causing gene mutations and could thereby be responsible for the association of (processed) red meat consumption with intestinal cancer. Up to now, neither in vitro nor in vivo studies characterizing the mutagenic and cell transforming potential of NO-heme have been published due to the fact that the pure compound is not readily available. Therefore, in the present study, an already existing synthesis protocol was modified to yield, for the first time, purified NO-heme. Thereafter, newly synthesized NO-heme was chemically characterized and used in various in vitro approaches at dietary concentrations to determine whether it can lead to DNA damage and malignant cell transformation. While NO-heme led to a significant dose-dependent increase in the number of DNA strand breaks in the comet assay and was mutagenic in the HPRT assay, this compound tested negative in the Ames test and failed to induce malignant cell transformation in the BALB/c 3T3 cell transformation assay. Interestingly, the non-nitrosylated heme control showed similar effects, but was additionally able to induce malignant transformation in BALB/c 3T3 murine fibroblasts. Taken together, these results suggest that it is the heme molecule rather than the NO moiety which is involved in driving red meat-associated carcinogenesis.

scholarly journals Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Rajeswari Jinka ◽  
Renu Kapoor ◽  
Pavana Goury Sistla ◽  
T. Avinash Raj ◽  
Gopal Pande
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Cell Transformation ◽  
Tumor Model ◽  
Genetic Alterations ◽  
Model Systems ◽  
Transformed Cells ◽  
Normal Cells ◽  
Multistep Process ◽  
Extracellular Matrix Interactions

Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems.

scholarly journals Involvement of Autophagy in Oncogenic K-Ras-induced Malignant Cell Transformation

2011 ◽  
Vol 286 (15) ◽  
pp. 12924-12932 ◽  
Author(s):  
Min-Jung Kim ◽  
Soo-Jung Woo ◽  
Chang-Hwan Yoon ◽  
Jae-Seong Lee ◽  
Sungkwan An ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Malignant Cell ◽  
Malignant Cell Transformation
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