Tumor cells are characterized by uncontrolled growth, invasion to surrounding tissues, and metastatic spread to distant sites. Mortality from
cancer is often due to
metastasis since surgical removal of
tumors can enhance and prolong survival. The
integrins constitute a family of transmembrane receptor
proteins composed of heterodimeric complexes of noncovalently linked alpha and beta chains.
Integrins function in cell-to-cell and cell-to-extracellular matrix (ECM) adhesive interactions and transduce signals from the ECM to the cell interior and vice versa. Hence, the
integrins mediate the ECM influence on cell growth and differentiation. Since these properties implicate
integrin involvement in cell migration, invasion, intra- and extra-vasation, and platelet interaction, a role for
integrins in
tumor growth and
metastasis is obvious. These findings are underpinned by observations that the
integrins are linked to the actin cytoskeleton involving
talin,
vinculin, and
alpha-actinin as intermediaries. Such cytoskeletal changes can be manifested by rounded cell morphology, which is often coincident with
tumor transformation via decreased or increased
integrin expression patterns. For the various types of
cancers, different changes in
integrin expression are further associated with
tumor growth and
metastasis.
Tumor progression leading to
metastasis appears to involve equipping
cancer cells with the appropriate adhesive (
integrin) phenotype for interaction with the ECM.
Therapies directed at influencing
integrin cell expression and function are presently being explored for inhibition of
tumor growth,
metastasis, and angiogenesis. Such therapeutic strategies include anti-
integrin monoclonal antibodies, peptidic inhibitors (cyclic and linear),
calcium-binding protein antagonists,
proline analogs, apoptosis promotors, and
antisense oligonucleotides. Moreover, platelet aggregation induced by
tumor cells, which facilitates metastatic spread, can be inhibited by the
disintegrins, a family of
viper venom-like
peptides. Therefore, adhesion molecules from the
integrin family and components of angiogenesis might be useful as
tumor progression markers for prognostic and for diagnostic purposes. Development of
integrin cell expression profiles for individual
tumors may have further potential in identifying a cell surface signature for a specific
tumor type and/or stage. Thus, recent advances in elucidating the structure, function, ECM binding, and signaling pathways of the
integrins have led to new and exciting modalities for
cancer therapeutics and diagnoses.