Cancer is infamous for being both difficult to detect and treat. That's largely because, unlike other diseases, tumors are not made up of an invading party. Instead, cancer is all about cells in the human body going rogue. Now researchers have highlighted a new way in which to assess why cancerous cells break nature's rules - a perspective that could help them think up new ways to keep diseases in check.

So just what are these 'rules' of cell life that cancer cells don't seem to be following? Experts have long suspected that all complex multicellular life forms are made up of cells that seem to adhere to the same guidelines, despite radical differences in structure and when they first appear in the fossil record. This is not unlike how, despite historical and cultural differences, most cities around the world function in remarkably similar ways.

Now, in a special issue of the journal Philosophical Transactions of the Royal Society of London B, a team led by experts from the Institute for Advanced Study, Wissenschaftskolleg, in Berlin, has outlined five basic concepts under which multicellular forms thrive.

"The idea of the five foundations really builds on decades of work in the field of multicellularity evolution," Athena Aktipis, a researcher at Arizona State University who was involved in the study, explained in a statement.

The Terrible Two

She described how the first of these foundations is the inhibition of cell proliferation, or population control. As you may already know, cells within the human body are constantly dividing, making new copies of themselves to replace the old ones. However, if left unchecked, it is very possible that healthy cells could reproduce too quickly, eventually turning an organism into a freakish lump not unlike a colony of bacteria.

That's where inhibition comes into play, restricting how many cells are alive at one time. This also goes hand-in-hand with the second foundation: regulation of cell death. Oftentimes, when a cell has outlived its usefulness, it will commit apoptosis - also known as "cellular suicide." This ensures a healthy body is functioning only with fresh and ready cells.

According to Aktipis and her colleagues, it's these first two foundations that experts pay the most attention to when investigating cancer. After all, cancerous cells are known to rapidly reproduce, growing harmful tumors rife with sick and damaged cells that refuse to slip quietly into the night. (Scroll to read on...)

Cheaters in the City

However, these are not the only cellular laws that cancer cells break in their multicellular 'cities.' Division of labor - determining where each cell belongs to form organs and flesh - is another guideline these rogue cells refuse to follow. Likewise, the researchers outlined how 'good' cells are always involved in resource transportation and the creation and maintenance of the extracellular environment. Without these three foundations - an almost economic system born of cellular cooperation - multicellular organisms ranging from fungi to humans could never have survived. Likewise, rule-breaking cells disrupting these foundations is what wreaks havoc in a cancer patient's body.

"For us, putting together the hallmarks of cancer with the foundations of multicellularity suggested that maybe these more economic forms of cheating have been neglected as components of cancer and contributors to cancer progression," Aktipis said. "Potentially we may be able to do better by creating diagnostics and measures of those types of economic cheating."

Why Cancer is no Tree Hugger

Additionally, while the study found evidence of the five foundations of multicellularity across the tree of life, it is clear that mechanisms for suppressing cheating are not equally divided among all life forms. Animals, it seems, are more susceptible to cancers than plants or complex microbes.

The study suggests that this may have a lot to do with the complexity of those last three foundations, as animals have far more organs and processes to maintain than your run-of-the-mill flower. Likewise, Aktipis and her colleagues add that more and varied interaction between cells and the outside world could further raise cancer risks. (Scroll to read on...)

Trees and even microorganisms tend to stay in the same environment their entire existence. Animals, however, are constantly changing what their cells are exposed to and how these iterations influence the cellular 'economy.' If you suddenly keep changing the nuances of a city's rules on its citizens, there are bound to be some who grow confused or fed up with it all. Thus cheaters, or cancer cells, are born.

"These things are important and perhaps underappreciated aspects of maintaining an effective multicellular body and suppressing cancer that would otherwise evolve," Aktipis added.

"This paper is a call to action for the evolutionary biology, comparative genomic and evolution of multicellularity communities to really come together and to collect data that will allow us to answer some of these big, outstanding questions about cancer suppression," she explained. "Together we can look to cancer across life for answers about the nature of cancer and new tools that can be used for cancer prevention in humans."

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