we consider non-genetic cell phenotype plasticity as a central process in therapy resistance. We take into account theability of cells to produce discretely distinct phenotypes, switch between them without genomic alterations and inherit the new
phenotype non-genetically across cell generations (Brock et al,2009).
Short answer: cancer cells can have different phenotypes depending on the matrix you put them on, not to mention if you alter the stiffness of the matrix you can also change their phenotype. Confluency is another factor that can alter cancer cell phenotype. I'm not entirely sure what you're trying to ask with your additional information but I hope that helps!
Hypoxia, chronic inflammation, and redox stress are the major factors which consist of the tumor micro-environment. Cancer cells exhibit epigenetic change to survive and proliferate under those unfavorable conditions. However, it depends on whether or not the epigenetic modifications are reversible or not.
Review paper to refer:
http://www.sciencedirect.com/science/article/pii/S1110863014000974
I remember that some one had done an experiment very long back injecting mice with melanoma cells. It resulted in melanoma secondaries in different organs. Cells from from the brain lesions were isolated and injected into other mice, which again produced lesions in various organs but more in brain. By repeating this sequence, melanoma cells (incidentally it is the cancer that has the highest propensity for brain metastasis) that metastasize only to the brain could be isolated (so calle soil and seed effect). Can you can this a 'phenotype' expression of the original malignant cell? ie., the original malignancy had cells with different phenotype. One is never sure of this because there may have been genotype differences too. I think in the case of cancer cell, there is not much sense in defining 'phenotypes'; even their genotypes can alter continously
Narayanan
I think we should consider and key words: expression, overexpression, metaregulation and Micro RNAs
Without genomic alterations, there are multiple mechanisms to regulate functional activity of numerous genes (and, finally, cell phenotype) - epigenetic regulation at the transcriptional (promoter methylation, chromatine structure etc) and post-transcriptional (miRNA) levels, physiological conditions (stress, hypoxia etc) and microenvironment...
Also, keep in mind that there are important functional systems which are regulated indirecly. For example, glycosylation - polysaccharide chains significantly contribute to (cancer) cell phenotype but they are synthesised on non-template basis by a complex system of biosynthetic enzymes. It means there are no genes for these chains and their biosynthesis completly depends on coordination and functional activities of the enzymes - so, deregulation of the system (non genetic) will result in changes in polysaccharide composition of the cells and modification of their phenotype...
Dear Dimple
Somehow I dislike the term plasticity (and elasticity) in relation to cell biology. Plasticity is a property that allows something to get deformed irreversibly; or in other words, Plastic resists deformation, but once deformed it is irreversible. Elasticity is the opposite, or Elastic does not resist change as much as plastic, but if it is changed, it is reversible. So what does plasticity in relation to cell and tissue really mean? I would say that functional tissues such as nerve tissue is plastic where as hierarchical tissues such as mucosa is plastic. And what does a plastic tumour really mean? I don't really get the hang of it ;-)
Narayanan
(PS Functional and hierarchical are subdivisions that clinical radiobiologists use)
Narayanan
Read this =D : British Journal of Cancer (2015) 112, 1725–1732 | doi: 10.1038/bjc.2015.146
yes! it's enough to remember imunosurveiance and imunoediting processes, other mechanisms trying to interrupt three main characteristics of cancerous cells( imortality-avoiding of apoptosis, invasion and unstopped proliferation;as a rule- simplest way of of ATP formation( glycolysis); simplest morphology. The scale of imunoinflamatory or metainflamatory processess is prognostic factor and condition of succes of therapies
Thanks Khalid. Dimple had already given that reference. I can only say again that the term plasticity in relation to tumours is meaningless in my opinion. A penchant for new terminologies results in unnecessary terminologies which can be quite confusing.
Let us take what plasticity means in the case of normal cells. To put it very simply, there are three types of mature cells produced in the bone marrow: RBC, WBC and Platelets. They all have a common ancestor, let us say Hemocytoblast. At some point, it gets committed to become one of the above and goes on in that pathway. Suppose there is a cell that is committed to become a WBC. But, because of some need or some change in the milieu, if it is able to revert back to a state that it can take change its path and mature into an RBC, then that cell may be said to have become plastic. (If no cell is committed to become RBC, then that person may be said to have aplastic anemia!) . This much is understandable and logical to me. You may also say that it had differentiated to WBC line, then de-differentiated and then redifferentiated to RBC line).
But when you say tumour cell is plastic, then what is an aplastic tumour. Or why not use a term, more understandable, with used words like differentiation.
As regards their finding, I agree that a tumour that you fail to eradicate in initial attempt becomes stronger. I have said this in all my papers uploaded in RG. Only it was in relation to radiotherapy and the same thing gets recognition when Medical Oncologists say this. And I would say that successful re-population attempts, due to insufficient dose, prolongation of interdose interval are the main cause in radiotherapy as well as chemotherapy
Narayanan
Yes- in cell culture systems especially with mixed cell populations ( for example breast cancer cells, fibroblasts and myoepithelial cells) the morphology of the cancer cells will alter depending on the ratio of the cells and also the in 2D versus 3D ( i.e gels) and also if in 3D the phenotype will be affected by the type of matrix used - coll IV v matrigel for example
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