Researchers Show That Genes Aren't Responsible For Cancer's Potential, But The Body's Culture Medium Is
A team of Boston University School of Medicine (BUSM) researchers have proposed that an "on and off" epigenetic switch could be a common mechanism behind the development of different types of cancer. The existence of this epigenetic switch is indirectly supported by the fact that tumors develop through different stages. When cells rapidly grow during cancer progression, they become stuck in their current stage of development and their cell characteristics do not change.
So what does change?
In the fields of infant nutrition, diabetes, obesity, and the metabolic syndrome, the term "metabolic programming" has been coined to give a name to the observation that environmental experiences early in life may be "genomically" remembered and give rise to health outcomes manifesting later in life. Epigenetics emerges as an important mechanism underlying this phenomenon.
Epigenetics is the phenomena whereby genetically identical cells express their genes differently, resulting in different physical traits. Researchers from the Boston University Cancer Center recently published two articles about this in Anticancer Research and Epigenomics.
The current paradigm states that cancer develops from environmental and genetic changes to cancer progenitor cells. These changes are the result of mutations, exposure to toxic substances or hormonal imbalances.
Cancer progression is extremely complex, however. It also is well known that new mutations and the activation of more cancer causing genes occur throughout the development and progression of cancer.
"If we believe that everything in nature occurs in an organized fashion, then it is logical to assume that cancer development cannot be as disorganized as it may seem," said Sibaji Sarkar, PhD, instructor of medicine at BUSM and the articles corresponding author. "There should be a general mechanism that initiates cancer progression from predisposed progenitor cells, which likely involves epigenetic changes."
Increasingly, biologists are finding that non-genetic variation acquired during the life of an organism can sometimes be passed on to offspring--a phenomenon known as epigenetic inheritance.
The majority of epigenetic changes occur at specific times in an individual's life, from their time in the womb, to the development as newborns, then in puberty, and again in old age.
Environmental factors that influence epigenetic patterns -- e.g., diet, epigenetic disruptors in the environment such as chemicals, etc. - may also have long term, multigenerational effects.
The existence of this epigenetic switch is indirectly supported by the fact that tumors develop through different stages. When cells rapidly grow during cancer progression, they become stuck in their current stage of development and their cell characteristics do not change. This is the reason that there are so many types of leukemia -- the characteristics that a leukemia cell possesses when it begins to rapidly grow and expand are the characteristics that it will keep until the rapid growth stops.
Dr. Lipton refers to the work of Dr. Dean Ornish to extrapolate. "Dr. Ornish has taken conventional cardiovascular patients, provided them with important lifestyle insights (better diet, stress-reduction techniques, and so on), and without drugs, the cardiovascular disease was resolved. Ornish relayed that if he'd gotten the same results with a drug, every doctor would be prescribing it."
Biologists have suspected for years that some kind of epigenetic inheritance occurs at the cellular level. The different kinds of cells in our bodies provide an example. Skin cells and brain cells have different forms and functions, despite having exactly the same DNA. There must be mechanisms--other than DNA--that make sure skin cells stay skin cells when they divide.
Even the strictest lifestyle changes don't cure cancer in everyone. What about genetic predispositions to getting the disease? "It used to be that we thought a mutant gene caused cancer," Lipton admitted, "but with epigenetics, all of that has changed."
Then he explained how his research revealed the science of epigenetics. "I placed one stem cell into a culture dish, and it divided every ten hours. After two weeks, there were thousands of cells in the dish, and they were all genetically identical, having been derived from the same parent cell. I divided the cell population and inoculated them in three different culture dishes.
"Next, I manipulated the culture medium--the cell's equivalent of the environment--in each dish. In one dish, the cells became bone, in another, muscle, and in the last dish, fat. This demonstrated that the genes didn't determine the fate of the cells because they all had the exact same genes. The environment determined the fate of the cells, not the genetic pattern. So if cells are in a healthy environment, they are healthy. If they're in an unhealthy environment, they get sick."
Dr. Lipton then took this a step further, which brings us back to the cancer question. "Here's the connection: With fifty trillion cells in your body, the human body is the equivalent of a skin-covered petri dish. Moving your body from one environment to another alters the composition of the ‘culture medium,' the blood. The chemistry of the body's culture medium determines the nature of the cell's environment within you. The blood's chemistry is largely impacted by the chemicals emitted from your brain.
Other than the brain, two other factors impact the fate of cells, according to Dr. Lipton: toxins and trauma. All three factors have been associated with the onset of cancer.
"If we believe that all of the irreversible changes, mutations and effects of carcinogens make cells rapidly grow, then the mechanism that allows cells to stop growing and assume new changes in character must be of great importance," added Sarkar. "The study of cancer progression is key to understanding how cancer cells continue to differentiate."During cancer progression, there are different stages of rapid growth and differentiation. The control that allows for this switch between growth and differentiation can only be achieved through reversible mechanisms, such as epigenetic changes.
Sarkar and colleagues have previously proposed that epigenetic changes are involved in cancer progenitor cell formation and cancer progression. They also believe that epigenetic changes have the ability to control rapid growth and change of characteristics (different grades/types of tumors) which may involve physiological processes that the cancer cells are subjected to within the body's terrain.
Sarkar compares the stages of cancer growth to a rocket orbiting in space -- that is, that an object within an orbit continues to circle a given path, until it is given a signal (or additional fuel) to propel itself into a further orbit. This comparison can be made for cancer progenitor cells and epigenetics. A specific cell continues to grow at a certain stage until it is given a signal -- in this case, an epigenetic switch -- that propels it to differentiate into a new orbit, or further differentiated cell.
The findings may deepen our understanding of the genetic changes that can lead to cancer and how these can be influenced by our diet and our environment. The findings can potentially open new ways of identifying, managing and treating cancer through lifestyle changes instead of conventional modes of treatment.