Cell division is a fundamental process that organisms need to replicate, expand, and make repairs. But when a mistake accomplishes this complex biological process, cellular abnormalities may lead to ailments, for example cancer, where cells are enabled to grow and divide out of control.

Their findings were published on April 29 at eLife, an open-access journal that is devoted to life science research.

Every individual'parent' cell holds two copies of each chromosome. Before cell division begins, each chromosome is duplicated so that the genetic information can be equally distributed between two'daughter' cells.

But if the parent cell fails to complete cell division, all four chromosomes are allocated into one daughter cell, thus producing the cell tetraploid.

When tetraploid cells acquire twice the number of chromosomes, they also acquire twice the number of centrosomes. One of their structural and organizational roles, centrosomes are key to forming microtubules and spindle fibers, which work to pull chromosomes apart during cell division.

Previous studies had indicated that these additional centrosomes might cause tumor formation, induced by tetraploidy.

But , the Virginia Tech team came across two studies in cancer progression models, which revealed that the cells gained extra centrosomes originally, but ended up losing them over time.

"The most important goal of our study was to confirm that tetraploid cells lose the extra centrosomes, analyze the dynamics of this process, and discover the mechanism that causes this centrosome loss from tetraploid cells," said Daniela Cimini, a professor in the Department of Biological Sciences and the co-director of BIOTRANS.

Using live cell imaging and fixed cell evaluation within an at vitro model, the team verified that tetraploid cells failed to shed the extra centrosomes they had obtained during tetraploidization.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://vtnews.vt.edu/articles/2020/06/fralinlifesci-cell-imaging-modeling-to-understand-cancer-progression.html">In experiments guided by mathematical modeling, they reasoned that centrosome reduction occurs when dividing tetraploid cells bunch their extra centrosomes asymmetrically.</a></span>
Because of this, among these female cells may inherit one centrosome - instead of two - that will permit the cell to endure fewer mobile division failures and create more cells at the long term.

This finding can describe how certain cancers can first gain additional centrosomes during tetraploidization, but then lose them at later stages. This implies that the causal relationship between tetraploidy and cancer requires further investigation.

The mathematical model additionally discovered that the cells that could sustain long-term survival with extra centrosomes were cells that could successfully and consistently cluster these centrosomes in two groups during cell division.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://vtnews.vt.edu/articles/2020/06/fralinlifesci-cell-imaging-modeling-to-understand-cancer-progression.html">These predictions were tested experimentally and revealed a mechanism which explains why certain cancer cells survive despite their additional centrosome count.</a></span>

And if cells failed to audience their extra centrosomes efficiently, another generation of daughter cells died.

"Built upon experimental measurements, the mathematical version paints a constant and detailed picture about the way the cells' centrosome numbers change"

"This allows us to see information that cannot be measured by experiments." Stated Chen, an affiliated faculty member of the Fralin Life Sciences Institute and BIOTRANS.

Then, the team might like to take advantage of their model to better understand the cellular dynamics inside three-dimensional cultures and actual tumors.

In their in vitro system, the group might get a sense of what was happening within the cells by tracking and imaging them, but that cannot be completed in much more complicated systems like actual tumors.

With their latest model and previous data, the team will have the ability to make some compelling predictions.

According to Chen, the achievement of current and prospective cancer studies could be attributed to a unique, but all significant, collaboration between researchers from the fields of biology and mathematics.

"This hand-in-hand collaboration between experimentalist and modeler is very important - and it's a fantastic approach for simulating biological studies"

"The procedure requires a whole lot of intimate communication between us. When that is done properly, it can be quite powerful," said Chen.
<div class="content-src-label"><strong>Source:</strong></div>
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<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://vtnews.vt.edu/articles/2020/06/fralinlifesci-cell-imaging-modeling-to-understand-cancer-progression.html" target="_blank" rel="noopener noreferrer">Virginia Tech</a></span>

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<div class="content-src-label"><strong>Journal reference:</strong></div>
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Baudoin, N<em>. C., et al. </em>(2020) Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells. <em>eLife</em>. <span style="color: #ff6600;"><a style="color: #ff6600;" href="https://doi.org/10.7554/eLife.54565" target="_blank" rel="noopener noreferrer">doi.org/10.7554/eLife.54565</a><em>.</em></span>

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