scholarly journals Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Eoin McEvoy ◽  
Yu Long Han ◽  
Ming Guo ◽  
Vivek B. Shenoy
Keyword(s):  
Gap Junctions ◽  
Cell Volume ◽  
Cancer Progression ◽  
Spatial Variations ◽  
Volume Control ◽  
Pressure Gradients ◽  
Multicellular Spheroids ◽  
Energy Consuming ◽  
Multiple Cells

AbstractSustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.

scholarly journals Gap Junctions Amplify Spatial Variations in Cell Volume in Proliferating Solid Tumors

2020 ◽  
Author(s):  
Eoin McEvoy ◽  
Yulong Han ◽  
Ming Guo ◽  
Vivek B. Shenoy
Keyword(s):  
Cell Proliferation ◽  
Gap Junctions ◽  
Cell Volume ◽  
Cancer Progression ◽  
Spatial Variations ◽  
Volume Control ◽  
Pressure Gradients ◽  
Multicellular Spheroids ◽  
Modeling Framework ◽  
Energy Consuming

AbstractCancer progression is driven by cell proliferation, apoptosis, and matrix invasion, which in turn depend on a myriad of factors including microenvironment stiffness, nutrient supply, and intercellular communication. Cell proliferation is regulated by volume, but in 3D clusters it remains unclear how multiple cells interact to control their size. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy consuming ion transporters, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, mechanical loading is shown to significantly affect how these components cooperate to transport ions, and precise volume control is impacted by the emergence of osmotic pressure gradients between cells. Consequent increases in cellular ion concentrations drive swelling, while a loss of ions impedes the compression resistance of cells. Combining the modeling framework with novel experiments, we identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model provides new insight into the role of gap junctions in cancer progression and can help guide the development of therapeutics that target inter- and extra-cellular ion transport.

scholarly journals Direct Intercellular Communications and Cancer: A Snapshot of the Biological Roles of Connexins in Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1370 ◽  
Author(s):  
Catalina Asencio-Barría ◽  
Norah Defamie ◽  
Juan C. Sáez ◽  
Marc Mesnil ◽  
Alejandro S. Godoy
Keyword(s):  
Gap Junctions ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Short Range ◽  
Tissue Homeostasis ◽  
Tunneling Nanotubes ◽  
Intercellular Communications ◽  
Precise Role ◽  
Intercellular Network

Tissue homeostasis is the result of a complex intercellular network controlling the behavior of every cell for the survival of the whole organism. In mammalian tissues, cells do communicate via diverse long- and short-range communication mechanisms. While long-range communication involves hormones through blood circulation and neural transmission, short-range communication mechanisms include either paracrine diffusible factors or direct interactions (e.g., gap junctions, intercellular bridges and tunneling nanotubes) or a mixture of both (e.g., exosomes). Tumor growth represents an alteration of tissue homeostasis and could be the consequence of intercellular network disruption. In this network, direct short-range intercellular communication seems to be particularly involved. The first type of these intercellular communications thought to be involved in cancer progression were gap junctions and their protein subunits, the connexins. From these studies came the general assumption that global decreased connexin expression is correlated to tumor progression and increased cell proliferation. However, this assumption appeared more complicated by the fact that connexins may act also as pro-tumorigenic. Then, the concept that direct intercellular communication could be involved in cancer has been expanded to include new forms of intercellular communication such as tunneling nanotubes (TNTs) and exosomes. TNTs are intercellular bridges that allow free exchange of small molecules or even mitochondria depending on the presence of gap junctions. The majority of current research shows that such exchanges promote cancer progression by increasing resistance to hypoxia and chemotherapy. If exosomes are also involved in these mechanisms, more studies are needed to understand their precise role. Prostate cancer (PCa) represents a type of malignancy with one of the highest incidence rates worldwide. The precise role of these types of direct short-range intercellular communication has been considered in the progression of PCa. However, even though data are in favor of connexins playing a key role in PCa progression, a clear understanding of the role of TNTs and exosomes is needed to define their precise role in this malignancy. This review article summarizes the current view of the main mechanisms involved in short-range intercellular communication and their implications in cancer and delves into the biological, predictive and therapeutic role of connexins in PCa.

Role of cytoskeleton in isotonic cell volume control of rabbit proximal tubules

1991 ◽  
Vol 261 (1) ◽  
pp. F60-F69 ◽  
Author(s):  
M. A. Linshaw ◽  
T. J. Macalister ◽  
L. W. Welling ◽  
C. A. Bauman ◽  
G. Z. Hebert ◽  
...  
Keyword(s):  
Cell Volume ◽  
Cytochalasin B ◽  
Renal Tubule ◽  
Proximal Tubules ◽  
Volume Control ◽  
Control Mechanisms ◽  
Volume Increase ◽  
Convoluted Tubules ◽  
Cell Volume Control

Stability of mammalian cell volume depends primarily on the sodium pump. When active cation transport of rabbit renal proximal tubules is blocked by ouabain, cells swell, but their size is limited by residual volume control mechanisms. This “ouabain-resistant” volume control is not an active process, as it operates in the presence of cyanide and dinitrophenol and in the absence of exogenous energy. Nevertheless, it remains incompletely explained by known transmembrane oncotic and hydrostatic forces. We tested the hypothesis that the cytoskeleton contributes to isotonic cell volume control. Isolated, collapsed rabbit proximal convoluted tubules (PCT) were crimped at both ends with micropipettes and had their volume assessed optically. PCT in ouabain (1 mM) swelled to 1.40 above control with protein, 1.62 without protein, and 1.89 with the cytoskeleton inhibitors vincristine (5 microM) and cytochalasin B (50 microM) and without protein. Tubulozole-C and cytochalasin D gave similar results. A hydrostatic pressure of 50 cmH2O increased tubule volume to 1.93 before the tubule basement membrane (TBM) prevented further volume increase. We conclude that volume of renal tubule cells in ouabain is limited partly by external protein, but primarily by the cytoskeleton. The TBM prevents massive swelling and tubule disaggregation.

scholarly journals Connexins and Gap Junctions in Cancer of the Urinary Tract

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 704 ◽  
Author(s):  
Thomas Tschernig
Keyword(s):  
Bladder Cancer ◽  
Urinary Tract ◽  
Gap Junctions ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Urinary Bladder Cancer ◽  
Gap Junctional Intercellular Communication ◽  
History Of ◽  
Gap Junctional

This review focuses on connexins and nexus or gap junctions in the genesis, progression, and therapy of carcinomas of the human urinary tract. Some decades ago, the idea was born that gap junctional intercellular communication might prevent both the onset and the progression of cancer. Later evidence indicated that, on the contrary, synthesis and the presence of connexins as a prerequisite for gap junctional intercellular communication might promote the occurrence of cancer and metastases. The research history of urinary bladder cancer is a good example of the development of scientific perception. So far, the role of gap junctional intercellular communication in carcinogenesis and cancer progression, as well as in therapeutical approaches, remains unclear.

Contribution of large bacteria to bacterial biomass in a deep freshwater lake (Lake Biwa, Japan)

2020 ◽  
Vol 85 ◽  
pp. 131-139
Author(s):  
S Shen ◽  
Y Shimizu
Keyword(s):  
Cell Volume ◽  
Bacterial Cell ◽  
Lake Biwa ◽  
Bacterial Biomass ◽  
Spatial Variations ◽  
Freshwater Lake ◽  
Heterotrophic Nanoflagellates ◽  
Bacterial Productivity ◽  
Transmission Electron ◽  
Seasonal And Spatial Variations

Despite the importance of bacterial cell volume in microbial ecology in aquatic environments, literature regarding the effects of seasonal and spatial variations on bacterial cell volume remains scarce. We used transmission electron microscopy to examine seasonal and spatial variations in bacterial cell size for 18 mo in 2 layers (epilimnion 0.5 m and hypolimnion 60 m) of Lake Biwa, Japan, a large and deep freshwater lake. During the stratified period, we found that the bacterial cell volume in the hypolimnion ranged from 0.017 to 0.12 µm3 (median), whereas that in the epilimnion was less variable (0.016 to 0.033 µm3, median) and much lower than that in the hypolimnion. Additionally, in the hypolimnion, cell volume during the stratified period was greater than that during the mixing period (up to 5.7-fold). These differences in cell volume resulted in comparable bacterial biomass in the hypolimnion and epilimnion, despite the fact that there was lower bacterial abundance in the hypolimnion than in the epilimnion. We also found that the biomass of larger bacteria, which are not likely to be grazed by heterotrophic nanoflagellates, increased in the hypolimnion during the stratified period. Our data suggest that estimation of carbon flux (e.g. bacterial productivity) needs to be interpreted cautiously when cell volume is used as a constant parametric value. In deep freshwater lakes, a difference in cell volume with seasonal and spatial variation may largely affect estimations.

Sign in / Sign up

Export Citation Format

Share Document