The Hayflick limit, discovered by Leonard Hayflick, refers to the phenomenon where normal somatic cells (non-reproductive cells) can only divide a limited number of times (typically 40-60 times) before they stop dividing and enter a state called cellular senescence.
The telomere cap protects DNA during cell division, and each cycle shortens the telomeres. When a telomere gets too short, the cell can no longer divide, and it activates apoptosis, or programmed cell death. This process provides natural protection against the unregulated proliferation of cancer. Cellular age is not counted in years, but rather, in the number of times a cell replicates.
While normal cells are mortal, cancer cells are immortal; they, like bacteria, are not restrained by the Hayflick limit and can replicate indefinitely. Cancer cells produce an enzyme called telomerase, which increases the length of the telomeres at the end of chromosomes. Because the telomere cap never wears down, cells can keep on dividing as long as they like. This blocks both the natural cellular aging process (senescence) and timed cellular death (apoptosis. In a cell culture, you can keep growing cancer cells forever.
In what is now a well-known story, our understanding of cancer owes a tremendous debt to a woman named Henrietta Lacks. On October 4, 1951, Lacks died of cervical cancer at Johns Hopkins Hospital at the age of thirty-one. The cancerous cells removed from her body-without her consent, it should be noted- have since revolutionized medicine. For the first time, scientists propagated a cell line outside a human body indefinitely. These HeLa cells, named after Lacks, have been used in the studies of vaccines, genetics, drug development, and cancer. More than fifty million tons of HeLa cells have been grown, and they have starred in more than sixty thousand scientific papers.
Normal cells, after reaching the Hayflick limit, cannot divide further. Cancer cells reproduce like digital files. You can transmit or replicate them with 100 percent fidelity to the original. From an organism’s perspective, killing off defective or old cell lines keeps things running smoothly. When your clothes develop holes over time, you need to throw them out and buy new ones.
Angiogenesis is the process of building new blood vessels, which brings in fresh supplies of oxygen and nutrients and carries away waste. As a tumor grows, new cells are situated farther from the blood vessels, just as new houses in a suburban subdivision are located farther from the main roads. New houses require the construction of new roads, and new cancer cells require the construction of new blood vessels.
Angiogenesis requires the close coordination of growth signaling of many different cell types. A breast tumor, for example, cannot simply keep making new breast cancer cells far from existing blood vessels. Somehow the cancer must induce the existing blood vessels to grow branches, just as new houses must connect their wastewater to the existing sewage system. This involves growing new smooth muscle cells, connective tissue, and endothelial cells (lining), an incredibly complex task that must be accomplished for a tumor to grow.
The ability to invade other tissues and metastasize is what makes cancer lethal, responsible for an estimated 90 percent of cancer deaths. Once these metastases are established, it matters little what happens to the original tumor. Cancers that cannot metastasize are called benign because they are easily treated and almost never cause death.
Metastasis is perhaps the most difficult hallmark to achieve, requiring completion of multiple complex intervening steps. A metastatic cancer cell must first break free of its surrounding structure, where it is normally held together tightly by adhesion molecules. That’s why you don’t usually find breast cells floating around in the blood or the lung, for example.
The freed cancer cell must survive the journey through the bloodstream and then colonize the metastatic site, a foreign environment completely different from its home. At each step along the metastatic pathway, the cancer cell acquires entirely new skill sets of incredible complex-ity, requiring multiple genetic mutations of existing pathways. It’s like humans trying to walk on the surface of Mars without a spacesuit and expecting to flourish.
Classically, we consider metastasis to transpire late in the natural history of cancer, after a lengthy growth period of the primary tumor. We’ve long assumed that the cancer stayed relatively local and intact until it started shedding some cancer cells into the blood. However, newer evidence suggests that micro-metastases may be shed from the original cancer early on, but these sloughed-off cells typically do not survive.
Cells need a reliable source of energy for the hundreds of routine housekeeping tasks they undertake every day. Cellular energy is stored in a molecule called adenosine triphosphate, or ATP. There are two ways to metabolize glucose for energy: with oxygen (aerobic respiration) and without oxygen (anaerobic fermentation). A chemical process called oxidative phosphorylation, or OxPhos, is the most efficient method of energy extraction.
This process burns glucose and oxygen together to generate thirty-six ATP molecules as well as a waste product, carbon dioxide, which is exhaled. OxPhos occurs in a part of the cell called the mitochondria, which are often referred to as a cell’s “power plants.”
When oxygen is not available, cells burn glucose using a chemical process called glycolysis, which generates only two ATP molecules, along with waste in the form of lactic acid. In the appropriate circumstance, this is a reasonable tradeoff-generating ATP far less efficiently, but without the need for oxygen. For example, high-intensity exercise such as sprinting requires large amounts of energy. Blood flow is insufficient to deliver the oxygen needed, so muscles instead use anaerobic (without oxygen) gly-colysis. The lactic acid generated is responsible for the familiar muscle burn upon heavy physical exertion. This creates energy in the absence of oxygen, but generates only two ATP molecules per glucose molecule instead of thirty-six. Thus, you cannot sprint very far before your muscles tire and you must stop to rest. When blood flow becomes sufficient to clear away the lactic acid buildup, you start to recover.
For every glucose molecule, you can generate eighteen times more energy with mitochondrial OxPhos compared to glycolysis. Because of this increased efficiency, normal cells almost always use OxPhos if sufficient oxygen is available. But cancer cells, strangely, do not. Cancer cells, almost universally, use the less efficient glycolytic pathway even in the presence of adequate oxygen.
Source : The Cancer Code: A Revolutionary New Understanding of a Medical Mystery by Jason Fung
Goodreads : https://www.goodreads.com/book/show/52163526-the-cancer-code
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