cell news 2/2013
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physics of cancer
thickness) and thus, mechanical properties between the various
parts of the body are different. In tumors, the microenvironment
is altered compared to “healthy” normal connective tissue: for
example the stiffness of the extracellular matrix and resulting
tissue deformations are almost modest in cancerous tissue and
serve as mechanical marker for primary or secondary tumors. A
mechanical parameter of the extracellular matrix is the stiffness,
which is a measure of the resistance exhibited by the elastic ex-
tracellular matrix upon deformation. The mechanical properties
of the extracellular matrix are important in regulating the func-
tional behavior of cancer cells by inducing mechano-sensitive
signaling pathways. During the malignant progression of cancer
the biomechanical homeostasis of the tissue is often deregula-
ted, and tumors exhibit increased stiffness compared to “healthy”
normal tissues (11). The increased stiffness of tumors alters the
tensional homeostasis of cancer cells and increases their ability
to transmit and generate contractile forces (11). An increase in
the stiffness of the extracellular matrix of connective tissue has
been implicated in tumorigenesis and thus the interaction of a
tumor with its stroma may shed light on the process of malig-
nant tumor progression. In contrast, the optical deformability of
cancer cells determined by using an optical stretcher device is
increased in metastatic cancer cells compared to “healthy” cells,
but consistent to Paszek et al. the cellular contractility is increa-
sed in metastatic cancer cells compared to “healthy” normal cells
(12). However, the interaction of mechanical and biochemical
signals of the matrix and cancer cells and how this is connected
to genetic and epigenetic alterations in tumor progression and
metastasis is still elusive. Finally, one question remains still open:
How may this connection between mechanical, biochemical and
genetic processes contribute substantially to the understanding
of tumor progression? How will this knowledge renew the cur-
rent view dramatically and the classical proposed hallmarks (13-
14), which defnitely exclude the mechanical properties of all
components involved: the cancer cells, neighboring cells and the
extracellular matrix microenvironment (13)?
Revealing its physical nature the extracellular matrix senses
cancer cells for alterations in stiffness by inducing mechano-
regulatory pathways. One important molecule in acting as a
mechano-sensor is vinculin (8-9). In particular, cells are able to
adhere to the extracellular matrix of connective tissue through
cell-matrix adhesion molecules. All cell-matrix adhesions con-
tain integrins as their major transmembrane receptors (16-17),
which are able to transmit forces (protrusive forces or adhesive
forces) derived from the microenvironment to the interior of the
cell, and in turn cytoskeleton-generated forces are exerted to the
exterior microenvironment. Compared to stationary cells, which
are frmly adhered to the extracellular matrix components and
where external and internal forces are of the same amount and
lead to non-polarized cells, motile cells are characterized by an
unequal force distribution, which polarizes the cell by promo-
Secondary tumor
Secondary tumor
Primary tumor
Dissimination of
cancer cells
Transendothelial
migration
(Extravasation)
Adhesion
Invasion
Invasion
Transport via blood-
or lymph vessels
Transendothelial migration
(Intravasation)
Metastasis formation
Basement
membrane
extracellular
matrix
Adhesion
Figure 1: Steps of malignant
progression of cancer.
Cancer cells spread from the
primary tumor and invade into
the extracellular matrix of
connective tissue. Some cancer
cells transmigrate through the
endothelial cell layer of blood
or lymph vessels including the
basement membrane and are
transported through the whole
body. Then, circulating cancer
cells have two possibilities: one
possibility is that cancer cells
adhere to the endothelium and
form a secondary tumor in the
lumen of the vessel. The second
possibility is that the cancer
cells transmigrate through the
endothelial cell lining and the
basement membrane into the
connective tissue of targeted
organs and form a secondary
tumor (so-called process of
metastasis).
