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 Over-Expression of βII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Kseniya Ruksha ◽  
Artur Mezheyeuski ◽  
Alexander Nerovnya ◽  
Tatyana Bich ◽  
Gennady Tur ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Cancer Progression ◽  
Nuclear Localization ◽  
Cancer Growth ◽  
Transformed Cells ◽  
Regulatory Pathway ◽  
Cell Nuclei ◽  
Normal Cells ◽  
Over Expression

Tubulin is a heterodimer of α and β subunits, both existing as isotypes differing in amino acid sequence encoded by different genes. Specific isotypes of tubulin have associations with cancer that are not well understood. Previous studies found that βII-tubulin is expressed in a number of transformed cells and that this isotype is found in cell nuclei in non-microtubule form. The association of βII expression and its nuclear localization with cancer progression has not previously been addressed. We here used a monoclonal antibody to βII to examine patients with colorectal cancer and found that patients whose tumors over-express βII have a greatly decreased life expectancy which is even shorter in those patients with nuclear βII. Our results suggest that βII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. Furthermore, βII expression and localization could be a useful prognostic marker. We also found that βII appears in the nuclei of otherwise normal cells adjacent to the tumor. It is possible therefore that cancer cells expressing βII influence nearby cells to do the same and to localize βII in their nuclei by an as yet uncharacterized regulatory pathway.

scholarly journals LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTβR and activating NF-κB signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Feng Qu ◽  
Bin Zhu ◽  
Yi-Lin Hu ◽  
Qin-Sheng Mao ◽  
Ying Feng
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Model ◽  
Model Systems ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Lymph Node Status

Abstract Background Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context. Methods Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting. Results GC cells and tissues exhibited significant HOXA-AS3 upregulation (P < 0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC. Conclusion HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.

scholarly journals RasV12; scrib−/− Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions

2021 ◽  
Vol 22 (16) ◽  
pp. 8873
Author(s):  
Caroline Dillard ◽  
José Gerardo Teles Reis ◽  
Tor Erik Rusten
Keyword(s):  
Tumor Suppressor ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Human Cancer ◽  
Tumor Model ◽  
Model Systems ◽  
Host Interactions ◽  
Suppressor Mutations ◽  
New Concepts ◽  
Cells Of The Microenvironment

The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Drosophila melanogaster. Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic RasV12 and the loss of the tumor suppressor scribble in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the RasV12; scrib−/− tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell–cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.

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 Tumor-extracellular matrix interactions: Identification of tools associated with breast cancer progression

2015 ◽  
Vol 35 ◽  
pp. 3-10 ◽  
Author(s):  
Marta Giussani ◽  
Giuseppe Merlino ◽  
Vera Cappelletti ◽  
Elda Tagliabue ◽  
Maria Grazia Daidone
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Matrix Interactions ◽  
Extracellular Matrix Interactions

scholarly journals LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTβR and activating NF-κB signaling

2021 ◽  
Author(s):  
Feng Qu ◽  
Bin Zhu ◽  
Yi-Lin Hu ◽  
Qin-Sheng Mao ◽  
Ying Feng
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Model ◽  
Model Systems ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Lymph Node Status

Abstract Background: Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context. Methods: Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting.Results: GC cells and tissues exhibited significant HOXA-AS3 upregulation (P<0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC. Conclusion: HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.

Differences in Membrane Order between C 3 H 10 T1/2 Cells and Their Transformed Counterparts as Measured by EPR

1992 ◽  
Vol 47 (1-2) ◽  
pp. 148-154 ◽  
Author(s):  
G. F. Grossi ◽  
M. Durante ◽  
M. Napolitano ◽  
A. Lanzone ◽  
P. Riccardi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hyperfine Splitting ◽  
Cell Transformation ◽  
Lipid Analysis ◽  
Cell Types ◽  
Transformed Cells ◽  
Fatty Acids Composition ◽  
Normal Cells ◽  
Membrane Order ◽  
Mouse Embryo Fibroblasts

Abstract Membrane order of mouse embryo fibroblasts and their ionizing radiation and chemically transformed counterparts was investigated using EPR spectroscopy after labeling the membrane of the cells with the fatty acid spin label, 5-nitroxy stearic acid. The EPR spectra were recorded at temperatures ranging from 18 to 38 °C for both control and transformed cells. The distance between the outer hyperfine splitting (2 T′||), which is used as an indicator of membrane order, varies in these two cell types. Below 28 °C, 2T′II is higher in transformed fibroblasts than in normal cells, whereas above this temperature membrane order is the same. Lipid analysis as carried out by the measurement of the cholesterol/membrane proteins and sphingomyelin/lecithin ratios, showed no difference in the amounts of the main membrane rigidifiers. These findings suggest that cell transformation of mouse fibroblasts induced by radiation or chemicals may produce alterations in the cell membrane, as evidenced by variations in its order at low temperature. These measured differences are presumably not attributable to its fatty acids composition but to its glycoproteins content, since changes in membrane regidifiers were not observed between normal and transformed cells.

The Basis of Cell-to-cell Transformation in Paramecium Bursaria

1972 ◽  
Vol 11 (2) ◽  
pp. 601-609
Author(s):  
C. A. CULLIS
Keyword(s):  
Thermal Stability ◽  
Mating Type ◽  
Cell Transformation ◽  
Paramecium Bursaria ◽  
Transformed Cells ◽  
Cell Contact ◽  
Mating Types ◽  
Normal Cells ◽  
Type Transformation ◽  
Rna And Dna

A mating type transformation, involving cell-to-cell contact (abortive conjugation) in syngen 4 of Paramecium bursaria has been investigated. By autoradiography, transfer of material between the conjugants in normal and abortive conjugation has been shown to occur. The transfer of this material, which includes protein, RNA and DNA, during abortive conjugation has been shown to be necessary if the transformation is to occur. The mating type substances produced by sexually competent cells of different mating types have been characterized with respect to their thermal stability. In all cases examined there appeared to be 3 mating type substances produced which had different temperature stabilities. No differences could be shown between the transformed cells and normal cells of the same mating type in relation to stability of mating type substance.

SHCA PHOSPHOTYROSINE DERIVED SIGNALING IS REQUIRED FOR THE MAINTENANCE OF CARDIAC FUNCTION

2008 ◽  
Vol 31 (4) ◽  
pp. 23
Author(s):  
Rachel Vanderlaan ◽  
Rod Hardy ◽  
Golam Kabir ◽  
Peter Back ◽  
A J Pawson
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Function ◽  
Tyrosine Kinases ◽  
Sh2 Domain ◽  
Scaffolding Protein ◽  
Restricted Domain ◽  
Downstream Signaling ◽  
Matrix Interactions ◽  
Extracellular Matrix Interactions ◽  
Ptb Domain

Background: ShcA, a scaffolding protein, generates signalspecificity by docking to activated tyrosine kinases through distinct phosphotyrosine recognition motifs, while mediating signal complexity through formation of diverse downstream phosphotyrosine complexes. Mammalian ShcA encodes 3 isoforms having a modular architecture of a PTB domain and SH2 domain, separated by a CH1 region containing tyrosine phosphorylation sites important in Ras-MAPK activation. Objective and Methods: ShcA has a necessary role in cardiovascular development^1,2. However, the role of ShcA in the adult myocardium is largely unknown, also unclear, is how ShcA uses its signaling modules to mediate downstream signaling. To this end, cre/loxP technology was employed to generate a conditional ShcA allele series. The myocardial specific ShcA KO (ShcA CKO) and myocardial restricted domain mutant KI mice were generated using cre expressed from the mlc2v locus^3 coupled with the ShcA floxed allele and in combination with the individual ShcA domain mutant KI alleles^2. Results: ShcACKO mice develop a dilated cardiomyopathy phenotype by 3 months of life, typified by depressed cardiac function and enlarged chamber dimensions. Isolated cardiomyocytes from ShcA CKO mice have preserved contractility indicating an uncoupling between global heart function and single myocyte contractile mechanics. Force-length experiments suggest that the loss of shcAmediates the uncoupling through deregulation of extracellular matrix interactions. Subsequent, analysis of the ShcA myocardial restricted domain mutant KImice suggests that ShcA requires PTB domain docking to upstream tyrosine kinases and subsequent phosphorylation of the CH1 tyrosines important for downstream signaling. Conclusion: ShcA is required for proper maintenance of cardiac function, possibly regulation of extracellular matrix interactions. References: 1. Lai KV, Pawson AJ. The ShcA phosphotyrosine docking protein sensitizescardiovascular signaling in the mouse embryo. Genes and Dev 2000;14:1132-45. 2. Hardy WR. et al. Combinatorial ShcA docking interactions supportdiversity in tissue morphogenesis. Science2007;317:251-6. 3.Minamisawa, s. et al. A post-transcriptional compensatory pathway inheterozygous ventricular myosin light chain 2-deficient mice results in lack ofgene dosage effect during normal cardiac growth or hypertrophy. J Biol Chem 1999;274:10066-70.

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