scholarly journals Microenvironmental factors in cell segregation and heterogeneity in breast cancer development

2021 ◽  
Author(s):  
J. Roberto Romero-Arias ◽  
Carlos A. González-Castro ◽  
Guillermo Ramírez-Santiago

ABSTRACTWe analyzed a quantitative model that describes the epigenetic dynamics during the growth and evolution of an avascular tumor. A gene regulatory network (GRN) formed by a set of ten genes that are believed to play an important role in breast cancer development was kinetically coupled to the microenvironmental agents: glucose, estrogens and oxygen. The dynamics of spontaneous mutations was described by a Yule-Furry master equation whose solution represents the probability that a given cell in the tissue undergoes a certain number of mutations at a given time. We assumed that mutations rate is modified by nutrients spatial gradients. The tumor mass was grown by means of a cellular automata supplemented with a set of reaction diffusion equations that described the transport of the microenvironmental agents. By analyzing the epigenetic states space described by the GRN dynamics, we found three attractors that were identified with the cellular epigenetic states: normal, precancer and cancer. For two-dimensional (2D) and three-dimensional (3D) tumors we calculated the spatial distributions of the following quantities: (i) number of mutations, (ii) mutations of each gene and, (iii) phenotypes. Using estrogens as the principal microenvironmental agent that regulates cells proliferation process, we obtained the tumor shapes for different values of the estrogen consumption and supply rates. It was found that he majority of mutations occurred in cells that were located close to the 2D tumor perimeter or close to the 3D tumor surface. Also It was found that the occurrence of different phenotypes in the tumor are controlled by the levels of estrogen concentration since they can change the individual cell threshold and gene expression levels. All the results were consistently observed for 2D and 3D tumors.

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 16-18
Author(s):  
Chia-Chien Hsieh

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.


Author(s):  
Giovanna Cassone Salata ◽  
Isabella D. Malagó ◽  
Vanessa F. M. Carvalho Dartora ◽  
Ana Flávia Marçal Pessoa ◽  
Márcia Carvalho de Abreu Fantini ◽  
...  

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