Springer, Encyclopedic Reference Of Cancer (2001) Ocr 7.0 Lotb.pdf

26 Adhesion
Adhesion. Table ± Adhesion Receptors
family main members type of adhesion
integrins characterized by the different
a- and b-subunits
IgG superfamily ICAM-1, V-CAM, N-CAM,
CD2 (LFA2), LFA3, CD4, CD8,
MHC (class I and II)
(by loss of activity of the cyclinE/cdk2 complex)
and undergo apoptosis (anoikis).
Transformed cells, in which integrin signaling
is altered, acquire the ability to grow in
suspension and do not succumb to anoikis.
* Adhesion to neighboring cells, mediated by
cell-cell adhesion molecules (e.g. N-CAM
and C-CAM) and by gap-junctions, inhibits
growth of normal cells (what is commonly
known as `contact growth inhibition').
Loss of these contacts due to the disrupted
function of the relative adhesion molecules
may result in uncontrolled proliferation.
* The differentiated state of mature cells (their
`identity') is also maintained through specific
adhesion to the ECM and adjacent cells: a
loss of identity is thus a likely consequence if
specific contacts are lost, finally resulting in
the ambiguous phenotype of many tumor
cells.
Certain genes that code for cell adhesion molecules
may therefore be considered as ! tumor
suppressor genes or even ! metastasis suppressor
genes since their loss or a functional mutation
can strongly contribute to the acquisition of the
malignant phenotype.
Adhesion in metastasis
cell-ECM
cell-cell
cell-ECM
cell-cell
cadherins E, P, L cell-cell
(adherens junction)
selectins E, P, N cell-cell
connexins 26 (tumor suppressor)
32 (liver)
43 (glial cells)
cell-cell
(gap junctions)
cell surface proteoglycans syndecan, glypican cell-ECM
cell-cell
CD44 CD44s, CD44v cell-ECM
cell-cell
Adhesive interactions play a very critical role in
the process of metastatic tumor dissemination,
and the abnormal adhesiveness that is generally
displayed by tumor cells appears to contribute
to their metastatic behavior. Both positive and
negative regulation of cell adhesion are required
in the metastatic process, since metastatic
cells must break away from the primary
tumor, travel in the circulation where they can
interact with blood cells and then adhere to cellular
and extracellular matrix elements at specific
secondary sites.
Adhesion within the tumor mass
The majority of normal adult cells are restricted
by compartment boundaries that are usually
conserved during the early stages of development
of a tumor. Therefore, the detachment
of malignant cells from the primary tumor is
an essential step for the initiation of the metastatic
cascade. During ! tumor progression
changes on the cell surface that lead to a weakening
of the cellular constraints, contribute to
the release of such mutant cells from the primary
tumor mass. Indeed, it was found that tu-