Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1098 Chapter 20: Cancer
Cancer Cells Display an Altered Control of Growth
Mutability and large cell population numbers create the opportunities for mutations
to occur, but the driving force for development of a cancer has to come from
some sort of selective advantage possessed by the mutant cells. Most obviously,
a mutation or epigenetic change can confer such an advantage by increasing the
rate at which a clone of cells proliferates or by enabling it to continue proliferating
when normal cells would stop. Cancer cells that can be grown in culture, or cultured
cells artificially engineered to contain the types of mutations encountered
in cancers, typically show a transformed phenotype. They are abnormal in their
shape, their motility, their responses to growth factors in the culture medium,
and, most characteristically, in the way they react to contact with the substratum
and with one another. Normal cells will not divide unless they are attached to the
substratum; transformed cells will often divide even if held in suspension. Normal
cells become inhibited from moving and dividing when the culture reaches confluence
(where the cells are touching one another); transformed cells continue
moving and dividing even after confluence, and so pile up in layer upon layer in
the culture dish (Figure 20–11). In addition, transformed cells no longer require
all of the positive signals from their surroundings that normal cells require.
Their behavior in culture gives a hint of the ways in which cancer cells may
misbehave in their natural environment, embedded in a tissue. But cancer cells in
the body show other peculiarities that mark them out from normal cells, beyond
those just described.
Cancer Cells Have an Altered Sugar Metabolism
Given sufficient oxygen, normal adult tissue cells will generally fully oxidize
almost all the carbon in the glucose they take up to CO 2 , which is lost from the
body as a waste product. A growing tumor needs nutrients in abundance to provide
the building blocks to make new macromolecules. Correspondingly, most
tumors have a metabolism more similar to that of a growing embryo than to that
of normal adult tissue. Tumor cells consume glucose avidly, importing it from the
blood at a rate that can be as much as 100 times higher than neighboring normal
cells. Moreover, only a small fraction of this imported glucose is used for
production of ATP by oxidative phosphorylation. Instead, a great deal of lactate
is produced, and many of the remaining carbon atoms derived from glucose are
diverted for use as raw materials for synthesis of the proteins, nucleic acids, and
lipids required for tumor growth (Figure 20–12).
This tendency of tumor cells to de-emphasize oxidative phosphorylation even
when oxygen is plentiful, while at the same time taking up large quantities of
glucose, can be shown to promote cancer cell growth and is called the Warburg
contact-inhibited monolayer
of normal cells in
tissue-culture dish
transformed cells
lose contact inhibition
foci of uninhibited
transformed cells
(A)
(B)
CELL
TRANSFORMATION
(C)
CELL
DIVISION
Figure 20–11 Loss of contact inhibition
by cancer cells in cell culture. Most
normal cells stop proliferating once they
have carpeted the dish with a single layer
of cells: proliferation seems to depend
on contact with the dish, and to be
inhibited by contacts with other cells—a
phenomenon known as “contact inhibition.”
Cancer cells, in contrast, usually disregard
these restraints and continue to grow, so
that they pile up on top of one another,
as shown (Movie 20.2). (A) Schematic
drawing. (B and C) Light micrographs of
normal (B) and transformed (C) fibroblasts.
(B and C, courtesy of Lan Bo Chen.)