The Cell: Basic Structure and Function
Fig. 1.7 The cell cycle
and its morpholgical
appearance. (A) Schematic presentation of the cell
cycle. (B) Typical anaphase during mitosis of plant
cells. (C) Mitosis of transformed epithelial cells in
Normal epithelium
Single cells in complex organisms work in a hierarchical order
determined by their differentiation state. Each single cell ful-
fills its function through biochemical processes that are highly
regulated and act in well-orchestrated pathways. The outgrowth
of tumors occurs if the cells have lost the capability to follow
these predetermined rules. Growth restriction, a typical feature
of normal tissues, is lost; the capability to commit cellular sui-
cide (apoptosis) once certain death signals have been activated
is lost. Differentiation pathways that permit the cell to enter irre-
versible cell cycle arrest become disconnected. Mechanisms that
under normal conditions are required to maintain the normal
histological architecture of an organ are erroneously activated to
feed the outgrowing tumor with essential nutrients.
Tumors may be derived from more or less all human tis-
sues, including epithelium that may be transformed into benign
adenomas and malignant carcinomas, mesenchymal tissues
that may be transformed into benign fibromas and malignant
sarcomas, hematopoietic tissues that may be transformed into
lymphoma and leukemia, and finally even germ cells that may
be transformed into benign teratomas and malignant terato-
Benign lesions are partially growth restricted: They do not
invade, do not metastasize, but do grow locally. In contrast,
malignant tumors usually acquire more autonomous growth
properties, and develop complex strategies to invade other
organs, to disseminate their cells to distant anatomical sites, to
evade immunological attack of the host's immune system, and
to initiate from disseminated cells again autonomous prolifera-
tive metastatic lesions. Following the concept that all these fea-
tures are mediated by a complex network of genes, the question
arises what genes are regulating the process of growth control in
cancer cells and why are these genes activated or inactivated in
distinct somatic cells that thus acquire the capacity to grow out
as cancer cell. Evidently the modifications required to induce
benign tumors are by far less complex than those required
for an invasive cancer. They usually can be achieved by minor
Several early mutations lead to
epithelial cell expansion and
initial transformation
Defects in genes that control the
genetic homeostasis results in rapid
accumulation of many mutations
(genetic instability). Emergence of
cell clones that display genetic
instability is the key event required for
malignant transformation
Severe alterations of the gene expression
profile induced by the accumulating
mutations finally allow for invasive
metastatic growth
Normal cell
Transformed cell
Fig. 1.8 Transformation
of epithelial cells.
modifications of the genome of the affected cells. In many cases
benign tumors are therefore precursors of malignant tumors
that require a substantially more complex pattern of genetic
modifications (Fig. 1.8).
The biological phenotype of cancer cells is defined by
the expression of certain genes, whereas other genes are not
expressed. These phenotype-specific gene expression patterns
are referred to as "gene signatures" that differentiate a distinct
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