Can Animal Migration Explain Cancer Motility?
Biological principles govern how species, organisms and cancers develop and persist. Perhaps one of the best examples is the theory of natural selection, which is the adaptation of heritable traits selected for by an organism’s environment. In small incremental adaptations over the course of multiple generations, species develop ways to minimize such stress.
Cells abide by the same principles of natural selection that all organisms do. For cells, the selection pressure comes from the microenvironments found within an organism. In all organisms, cells are constantly surveyed for how fast and frequently they replicate, while unneeded cells are degraded by the immune system. Since the body is constantly killing cells, the body (or, more specifically, the immune system) can be categorized as the selection pressure on their own cells. If cells have accumulated the proper mutations that allow them to divide rapidly, evade the immune system, and gather their own nourishment — among other hallmarks — cancer develops.
As cancer continues to grow unchecked, it tries to gather more nutrients and space by invading surrounding tissue. The tumor grows until it reaches nearby lymphatic or blood vessels to get a direct source of nutrients. Cancer can also develop its own vasculature through a process known as angiogenesis. Once cancer has reached the surrounding vasculature, tumor cells have reached a direct route to anywhere in the body.
Cancer becomes more dangerous, and mortality rate dramatically increases when cancer is able to metastasize — when one tumor, termed the primary tumor, begins to send cells throughout the body to produce secondary colonies. Yet, each region of the body contains different microenvironments which could harm or benefit the cancers’ growth. But, if the primary tumor’s location is suitable then what is the motivation for metastasis? Dr. DeGregori asks this same question and answers it in his article How cancer shapes evolution, and how evolution shapes cancer with why do animals migrate? Such a question complicates how scientists view cancer, because cancer’s movement is not unique. Perhaps by looking at the principles of animal migrations, researchers may gain a better understanding for why cancer metastasizes.
The allocation of energy and nutrients towards one trait may have a negative affect on others. When cancer cells leave their primary tumors, for example, they will undergo a period of nutrient depletion which impacts their reproduction. The same can be said for birds in seasonal migration. Short-to-medium distance migratory birds can gain 10–25% of the body weight, and long-distance birds can double their weight prior to their travel. Rather than portioning these nutrients to other needed activities, like reproduction, cancer and animals have chosen to move location in an effort to have more nutrients in the future.
Dr. Jander categorizations this type of migration as one that:
“takes an organism beyond its home range, but still ceases when suitable resources are contacted. This type of movement has been called ‘ranging’, because it incorporates exploration of new areas and eventually the location of a new home range or place of residence” (Jander 1975).
This definition of animal migration can be connected to cancer metastasis. As a primary tumor continues to grow, it requires additional nutrients, blood supply and space. Cancer cells can take nutrients, growth factors and other supplies from neighboring stromal cells thus making their local environment damaging to healthy cells and outcompete them for survival. However, when the primary tumor inevitably outgrows the available resources or space, cancer cells will begin ‘ranging’ throughout the body to find a new area. Many of these cells will die as a result of different environmental conditions throughout the body. For instance, the mutations that allowed them to live in one environment, say the breast tissue, may not allow them to survive in a different environment, say the brain. So, the tumor is willing to sacrifice ranging cells to eventually find a suitable environment.
Yet, animals are faced with difficulty in migration and are able to make accommodations to decrease waste. When aphids were exposed to a strong wind, which was extrapolated to mean a strong pressure against migration, they would land earlier despite having a less suitable environment. Perhaps cancer does something similar. As stated by Dr. Joyce in her article Microenvironmental regulation of metastasis
“Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and grow”
At each of these steps, cancer cells are stymied by the immune system and neighboring cells, so cancer will settle at any location that they can grow in. Like aphids, cancer faces harsh selection pressure when it leaves the primary tumor and is therefore willing to settle in the closest location possible.
Additionally, more aggressive cancers are able to sacrifice cells to grow in different environments. Considering the principle of r-selected species, like mice which have a short lifespan but have a much higher fecundity rate, cancer rapidly divides to increase population size rather than survive for a longer period of time. This rapid division increases tumor size while cancer garners new mutations to eventually find ones suitable in new environments.
For a time, researchers argued that migration was a product of group selection — where selection pressures affect a population rather than individuals to achieve variation. Often, group selection is attributed to altruistic traits, like birds warning about a predator or early hominids performing collective hunting, however, evolutionary geneticists have more accurately attributed the evolution of migration to individual, heritable genetic variations. Perhaps the origin of animal migration may shed light on how metastatic cancer develops in an individual; moreover, is the entire primary tumor working together to become mobile, or is it particular cells that drive this change?
Likewise, metastatic cancer develops when primary cancer cells accumulate the appropriate mutations to survive in other environments. While research is contesting when a primary tumor develops into metastatic cancer, one research article by Dr. Mika Suzuki and Dr. David Tarin suggests metastasis is prevalent within the primary tumor and will leave its location under certain cues. In his paper, they genetically sequenced 10 patients with metastatic breast cancer and compared the genetic mutations of their primary tumors to their secondary lymphatic tumors. He found that across all of these patients the secondary tumors had the exact same genetic pool of mutations leading him to conclude that secondary tumors are established within the primary tumors and only moves to different tissues when primary tumors are disrupted or signaled to migrate only molecular cues.
