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.

Mammalian alpha-fetoproteln (AFP) Is classified as a member of the albuminoid gene superfamily consisting of albumin, AFP, vitamin D (Gc) protein, and alpha-albumin. Molecular variants of AFP have long been reported In the biomedical literature. Early studies Identified Isoelectrlc pH isoforms and lectin-binding variants of AFP, which differed In their physicochemical properties, but not In amino acid composition. Genetic variants of AFP, differing in mRNA kllobase length, were later extensively described in rodent models during fetal/perinatal stages, carcinogenesis, and organ regeneration. With the advent of monoclonal antibodies in the early 1980s, multiple antigenic epitopes on native AFP were detected and categorized, culminating In the Identification of six to seven major epltopes. During this period, various AFP-blndlng proteins and receptors were reported to inhibit certain AFP Immunoreactlons. Concomlttantly, human and rodent AFP were cloned and the amino acid sequences of the translated proteins were divulged. Once the amino acid composition of the AFP molecule was known, enzymatic fragments could be identified and synthetic peptide segments synthesized. Following discovery of the molten globule form In 1981,the existence of transitory, intermediate forms of AFP were acknowledged and their physiological significance was realized. In the present review, the various Isoforms and variants of AFP are discussed In light of their potential biological relevance.

alpha-fetoprotein has long been considered the 'gold-standard' in the field of tumor markers. During the several decades since the recognition of mammalian alpha-fetoprotein as a tumor-associated fetal protein, it has been purified, characterized, cloned and sequenced for use in the clinical diagnostic laboratory. However, the biological role of alpha-fetoprotein in the regulation of cancer growth has received comparatively little attention. Only during the last decade has the modulatory role of alpha-fetoprotein in neoplastic growth been realized and implemented in experimental models. This review examines the basis for the current consensus that alpha-fetoprotein does indeed regulate neoplastic growth through the presence of an alpha-fetoprotein cell surface receptor that undergoes internalization to the cell interior. Studies involving uptake of this fetal protein have since culminated in radio imaging reports as well as the use of alpha-fetoprotein as an anticancer drug conjugate. Finally, the therapeutic utilization of alpha-fetoprotein and its peptidic fragments as growth-response modifiers encompasses biological events, such as apoptosis G-coupled signal transduction, gene therapy, vaccination and cancer chemoprevention.