Probing life’s simplest organism to understand the complexity of cancer

Probing life’s simplest organism to understand the complexity of cancer

February 18, 2019

  • ASU scientists recently discovered that T. adhaerens, the simplest multicellular animal known to man, engages in social feeding behavior despite not having a nervous system. Researchers are studying the species to understand its mechanisms against developing cancer.

    Image credit: Angelo Fortunato


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February 18, 2019

The simplest multicellular animal known to man (Trichoplax adhaerens) has no nervous system, no muscle tissue, and, most importantly, no history of cancer. Typically, cancer is a disease afflicting multicellular organisms that spreads as cells grow and divide. Arizona State University researchers are looking to these small creatures to learn more about how they evade the deadly disease, and the implications this has for other multicellular animals.

At the Biodesign Center for Biocomputing, Security and Society, researchers Angelo Fortunato and Athena Aktipis decided to create a project focusing on the evolutionary habits of cancer and cancer-evaders. Discovered in the late 1960s, T. adhaerens is native to the Red Sea and other temperate waters. Fast-forward 50 years, and we now have its entire genome sequenced, allowing scientists to investigate the function of its genes. The quick growth cycle of T. adhaerens speeds up the rate of experiments, allowing answers to emerge rapidly at a low cost. The study was published by Frontiers in Ecology and Evolution on February 14.

The Biodesign team was surprised to discover that the primitive organism engages in social feeding behaviors, despite lacking muscles, nerves or a digestive system. The animals gather together in clusters to eat algae by secreting enzymes and then externally digesting nutrients. Although the reason for this is still unknown, Fortunato determined that the creatures were actively choosing to feed together. In the semi-natural habitat that the researchers set up in the lab for the animals to grow, scientists were able to observe how T. adhaerens formed tightly packed lines and moved in solidarity towards areas with an abundance of algae. This is the first record of social behavior in this species and was captured on camera by Fortunato. This discovery is potentially the most primitive case of social behavior ever described in a non-colonial animal and could predate the social behavior of previously described social animals by approximately 300 million years.

In his work with ASU’s new Arizona Cancer and Evolution Center (ACE), Fortunato is trying to gain a more comprehensive understanding of T. adhaerens and other cancer-resistant species. Researchers are trying to understand cancer across the tree of life, spanning from the smallest organisms to the largest. One day, scientists hope to turn the evolutionary toolsets of sponges, flatworms, and elephants into solutions for humans.

“We think that all multicellular organisms have to deal with the cancer problem, it’s not just a human problem,” Fortunato said. “There are cancers that affect basically every organism. Some of these organisms seem to be much more resistant than others. There must be something to help this animal fight and prevent cancer development.”

Part of the mission of ACE is figuring out how to “live with cancer,” rather than exposing the body to toxic chemicals in hopes of killing off mutated cells. Intensive medications can decrease the quality of life for patients undergoing treatments. Fortunato’s work with Aktipis and ACE Director Carlo Maley pushes the boundaries of cancer research—incorporating both cancer biology and evolutionary biology to find new solutions.

"Viewing cancer through an evolutionary and ecological lens offers researchers and physicians profound new insights and tools for both studying and controlling cancer,” said Maley, a professor in the School of Life Sciences.

“Rather than aggressive efforts to eradicate cancer, which may accelerate the evolution of treatment resistance and resurgence of the tumors, we are learning how to manage cancers so that we can live with the disease but not die from it.”

Before finding Maley and Aktipis at ASU, Fortunato searched around the world for the best place to incorporate his interdisciplinary passions into his work. Previously, he had struggled to convince classical labs to embrace a new approach to cancer studies. Fortunato found that traditional methods neglected the very nature of the disease being studied.

“If you don’t consider these cancer cells that are able to adapt and evolve, then it is very difficult to find a treatment because you are ignoring the basic biology of the cell,” Fortunato said. “I think that’s a major problem when these cells can mutate so quickly, and classic medicine can’t keep up.”

Fortunato’s latest studies examine how T. adhaerens reacts to DNA damage caused by radiation. Cancer-resistant species, like T. adhaerens and sponges, can withstand X-ray radiation at levels between 20 to 60 times greater than the common mouse. As they are exposed to X-rays, some genes associated with cancer are activated in T. adhaerens. Other genes, whose functions are not yet known, are also activated in the process. Fortunato looks for answers in the genes present in both human and non-human cells.

His next goal is to discover how T. adhaerens wards off genetic damage. Fortunato’s current research explores the defense system in place to block potentially dangerous cells from causing harm. At the tissue-level, T. adhaerens has a behavior mechanism that squeezes the damaged cells from within the surrounding tissue and kicks them out.

According to preliminary research, there is some suggestion that humans could do the same in certain organ tissues. Popular methods of cancer treatment today focus on attacking the disease at a molecular or immune level. However, it’s very easy for a few cells to survive treatment and continue to wreak havoc on patients’ health. Creating solutions at the tissue level is an intermediate possibility that could enhance existing therapies.

Fortunato believes the future of cancer treatment lies in the synchronization between different techniques and medications. Methods to prevent or control tumor growth could improve the efficacy of chemotherapy, surgery or immunotherapy, especially as cancerous cells evolve to resist drug treatment. By turning to mechanisms present in nature, Fortunato hopes to draw inspiration for the next wave of cancer solutions.

“I’m glad we’re taking a new approach to discovery,” Fortunato said.

 

Written by: Sabine Galvis