New study describes cancer's cheating ways

In some ways, cancer cells are like selfish people: They focus on their own goals, even at the expense of the greater good.

At least, that’s one way to summarize a new study that included Athena Aktipis, a researcher at Arizona State University’s Biodesign Institute. She, along with several international colleagues, helped author a paper that explores how cancers can bypass the protective mechanisms used by multicellular forms to ensure their survival and well-being.

In other words, cancer cells cheat by ignoring common strategies of cooperation to reach their goal. It’s a revelation that’s changing the understanding of cancer.

The study, which was conceived and largely written at the Institute for Advanced Study, or Wissenschaftskolleg, in Berlin, identifies five foundations of multicellularity:

• Inhibiting cell proliferation

• Regulation of cell death

• Division of labor

• Resource transport

• Creation and maintenance of the extracellular environment

“The idea of the five foundations really builds on decades of work in the field of multicellularity evolution,” Aktipis said, referring to a subfield of evolutionary biology concerned with such questions as how cells come together to form higher level entities that have functions of their own.

Without these mechanisms, multicellular organisms – from fungi to humans – could not have evolved into the endless forms we see today. Cancer cells, however, have the capacity to break free of this multicellular tyranny over their behavior.

As the authors note, research and clinical practice to date have focused primarily on the first two violations of the multicellular framework, namely limits to cell proliferation and regulation of cell death. In both cases, cancer appears capable of short-circuiting the built-in multicellular constraints, exhibiting the unchecked proliferation and growth characteristic of cancerous tumors.

The study compares the five foundations of multicellularity with so-called hallmarks of cancer, a set of underlying principles governing cancer behavior, proposed by researchers in 2000.

According to the cancer-hallmarks framework, cancer cells supply their own growth signals, resist inhibitory signals limiting their growth, resist programmed cell death (known as apoptosis), multiply indefinitely, stimulate blood vessels to supply tumors with nutrients (angiogenesis) and activate invasion of local tissues and the spread of cancer cells to distant sites (invasion and metastasis).

“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.”

Although 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. For instance, animals appear to be more susceptible to cancers than plants and other multicellular organisms. This may be due to higher metabolic rates that leave animals more vulnerable to cheating in resource allocation and division of labor, while animal circulatory systems may enhance an organism’s risk of metastasis.

“I think of it as the economics of multicellularity,” Aktipis said. “How do the resources get where they need to go, how does the labor get done that needs to get done to make the body work, how does the shared environment get taken care of and maintained? These things are important and perhaps underappreciated aspects of maintaining an effective multicellular body and suppressing cancer that would otherwise evolve.”

A greater focus on cancer’s subversion of the economic foundations of multicellularity may give rise to innovative new strategies for identifying cancer, charting its trajectory and fashioning effective treatments.

“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,” Aktipis said.

“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.”

Athena Aktipis is a researcher in the Biodesign Institute’s Center for Evolution and Medicine and assistant professor in ASU's Department of Psychology. Her forthcoming book is titled: "Evolution in the Flesh: Cancer and the Transformation of Life," published by Princeton University Press.

A longer version of this story can be found here.