Blood Supply And Tumor Growth - Chapter 1 Introduction To Preventing Cancer: Cancer

Content provided by the Faculty of the Harvard Medical School

Blood supply and tumor growth

A few damaged, erratic cells would not be dangerous in and of themselves. The problem is that, under the right circumstances, these cells begin to multiply out of control and form large tumors that have the potential to shed malignant cells that can spread to other parts of the body and wreak even more havoc. This final phase in the cancer process is known as progression.

A key event at this stage in the development of a cancerous tumor is the formation of new blood vessels, which ferry nutrients and growth factors to the colony of malignant cells, which then become a tumor. Almost every tissue in the body is laced with a network of small blood vessels that function like a sophisticated roadway system. Red blood cells carry nutrients and oxygen to keep tissues healthy and functioning, while other cells carry off waste products and other debris.

Normally, these vessels (known as capillaries) do not increase in size or quantity. But under some circumstances, new "roads" can be built. This is the case when you injure yourself. Bang your knee hard and it will likely turn red and swell up temporarily. This is an outward sign of what is happening beneath your skin: new blood vessels form to allow white blood cells, which are part of the immune system, to travel to the site of the injury, unleashing other cells that repair the damage. Once you have begun to heal, the temporary blood vessels disappear, and the swelling recedes.

Cancer cells unleash proteins that initiate angiogenesis, or they corrupt other cells, such as immune system macrophages, so that they release such proteins. These proteins are collectively known as proangiogenic growth factors. However angiogenesis originates, it results in the proliferation of blood vessels, which extend into the tumor and provide it with the nutrients, oxygen, and growth factors that will enable it to thrive.

Angiogenesis is so important to the growth of tumors that it has become a target in finding ways to stop cancer. Much of the work in this area was pioneered by the late Judah Folkman, M.D., a Harvard Medical School professor of pediatric surgery at Children's Hospital in Boston. Folkman and other researchers around the country researched the use of drugs, notably angiostatin and Endostatin, which, in animal studies, have shut down a tumor's blood supply. The purpose of these drugs is to destroy tumors by literally starving them of needed nutrients and oxygen.

Invasion of healthy tissue

Cancer is deadly because it can spread from wherever it originates to other parts of the body, crippling vital organs in the process. If cancer stayed in one place, treating it would be a matter of surgically removing the cancerous tissue as soon as it had grown big enough to detect. But once cancer cells begin to travel elsewhere in the body, the disease becomes much harder to obliterate.

Before cancer cells can actually travel through the bloodstream, they need to overcome a series of controls that normally force cells to stay put. The first hurdle is cell adhesion or anchorage. Normally, cells cannot replicate unless they are rooted in place - attached to another cell or to a type of scaffolding known as the extracellular matrix. Most cells will, in effect, commit suicide - the process of cell death known as apoptosis - if they cannot attach to one or the other.

A cancer cell seems to trick its own nucleus into believing that the cell is attached when it is not. How it does so is unclear, but scientists believe oncogenes, which help turn cells cancerous in the first place, may play a role by sending dummy signals to the nucleus. So cancer cells do not commit suicide, as they should, but instead become "anchorage independent," meaning they do not have to be attached to something in order to continue proliferating.

But this is only the first of several hurdles that cancer cells must overcome as they spread. Once detached, they penetrate a series of basement membranes - the layers of cells that surround a particular tissue like an enclosing glove and normally prevent other cells from getting in. So, for instance, a breast cancer cell first has to penetrate the basement membrane of breast tissue to get out, then must penetrate the basement membrane protecting a blood vessel so that it can reach the bloodstream itself. Once there, the cancer cell can travel elsewhere, but it cannot penetrate other tissue unless it once again overcomes the basement membranes of those tissues. This is not an easy process, and scientists believe that fewer than one cancer cell out of every 10,000 that actually reach your bloodstream will be able to attach itself in another part of your body.

Last updated:	May 01, 2008