[Dean's World] Dave Schuler: The Cancer Cells That Leave Home Have Extra DNA Capabilities

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Posted by Dave Schuler:
The Cancer Cells That Leave Home Have Extra DNA Capabilities
http://www.deanesmay.com/posts/1185914562.shtml


   by George L Gabor Miklos PhD and Phillip John Baird MD PhD

   The cells that leave the primary tumor have different DNA
   characteristics to those that remain. It is their altered properties
   that enable these emigrants to leave in the first place and for their
   descendants to infiltrate and destroy vital organs. (20, 21, 22, 30,
   31)

    Normal cells

   All normal cells have two copies of their DNA, one set from the mother
   and one set from the father. There are thus two DNA code books
   (instructions-for-cell-survival) in every normal cell. If one book is
   damaged, there is always a good copy from which to make repairs in an
   emergency. Normal cells carefully follow the instructions encoded in
   their DNA and execute them in a particular order and at specified
   times. Normal cells are tightly constrained by their two-book genetic
   operating manuals.

    Cancer cells

   By contrast, cancer cells that have left the primary tumor and are in
   transit or have arrived at their final destinations, have massively
   disrupted DNA contents. Their instructions-for-cell-survival books
   have been copied and they have more than two of them, but with
   profound differences. Enormous errors have occurred during the copying
   process so their books now contain some extra chapters, sentences and
   paragraphs, while some other chapters, paragraphs and sentences have
   been completely deleted. Furthermore, differing amounts of text have
   been shifted from one place to another and at the most basic level,
   single letters have been changed. These single letter changes are
   commonly referred to as mutations (6,32).

   The extent of these massive alterations in DNA is aptly described by
   Dr Garth Anderson, of the Roswell Park Cancer Institute in Buffalo,
   NY; "in most adult solid tumors the genome is shot to hell by the time
   the tumor is found..." and ...a mutation will not be in every cell in
   the tumor." (33)

    The danger lies in the diversity within a cancer cell population

   The mistake-prone process of DNA copying, cutting and pasting that
   goes on in cancer cells produces remarkable outcomes. Cancer cells no
   longer have to obey instructions. They have been liberated from the
   rigidity of conventional two-book genetic operating manuals. The
   ongoing process of massive alterations in DNA provides a cancer cell
   population with novel instructions on how to cope with various
   emergencies. Thus when chemotherapeutic drugs are encountered, some
   cancer cells in the population have different ways of dealing with
   drugs. No matter what defenses the body may deploy, some cancer cells
   in a population always have a new combination of instructions ready to
   face a crisis.

    The cancer cells that leave home have increased informational diversity

   The cancer cells that leave a primary tumor are often first found in
   the nearest lymph node draining the tumor and later in more distant
   places such as the bone marrow. A comparison of the DNA contents of
   individual cancer cells from the lymph nodes and bone marrow of the
   same patient to those of individual cells in the primary tumor reveals
   that cancer cells at these different locations have accumulated their
   own specific changes in their DNA contents. (22)

   The cancer cells that leave the primary tumor represent a diverse
   population upon which selection will act. Some cancer cells are
   destroyed by the immune system, others reach the lymph nodes and
   progress no further, whereas still others reach an organ but are held
   in check by the local resident cell population and cannot proliferate.
   Finally, some cancer cells survive all these hazards, grow at their
   new sites and ultimately destroy a vital organ. In a nutshell, this is
   metastatic cancer.

    Most cells in a primary tumor never leave

   Only a small number of the cells in a primary tumor ever develop the
   DNA alterations to emigrate (21,34,35). If all cells had the capacity
   to leave, no primary tumor would be left (21). When the cells of a
   primary tumor are tested both clinically and experimentally for their
   ability to form a new tumor, only approximately 1 in 50,000 cells has
   the capacity to do so (34-38). Only cells that have sufficiently
   altered genetic operating systems or stem cell-like properties (39-41)
   break free of the local constraints and depart. Normal cells always
   remain in their local neighborhood.

   (Next up: Drug Resistance and the Return of Cancer, and, New Frontier
   or Yet Another Unfulfilled Promise?--Dean)