title: Contribution of very late antigen-4 (VLA-4) integrin to cancer progression and metastasis.
abstract: The integrin "very late antigen-4" (VLA-4) is expressed by numerous cells of hematopoietic origin and possesses a key function in the cellular immune response, e.g., by mediating leukocyte tethering, rolling, binding, and finally transmigration of the vascular wall at inflammatory sites. Thus, VLA-4 is a valuable target in medical sciences to interfere with pathological inflammations. In addition, leukemic cells and different solid tumors, which express VLA-4, make use of these adhesive functions and confer VLA-4 a progressive role in the metastatic spread. With a growing insight into the molecular mechanisms for creating a tumor-friendly microenvironment at metastatic sites and various tumor host interactions, the multiple functions of VLA-4 became evident recently, e.g., in leukocyte recruitment to micrometastases, the protection of tumors from immune surveillance, or contribution to a chemoresistance. Nevertheless, despite accumulating evidence for several functions of VLA-4 in tumorigenicity, a therapeutic interference with VLA-4 in cancer sciences has not been developed yet to the clinical level, undoubtedly by a marked impact on the physiological immune response. This review gives an up to date insight into the multiple functional role of VLA-4 in cancer and introduces this integrin as a promising target worthwhile to attract attention in biomedical cancer research.
authors.affiliation: Department of Pharmacy, Rheinische Friedrich-Wilhelms-University Bonn, An der Immenburg 4, 53121, Bonn, Germany. martinschlesinger1@gmx.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlesinger
authors.affiliation: Department of Pharmacy, Rheinische Friedrich-Wilhelms-University Bonn, An der Immenburg 4, 53121, Bonn, Germany. gbendas@uni-bonn.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Bendas
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D059016:Tumor Microenvironment; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1
keywords: Angiogenesis; Cancer; Integrin; Metastasis; VCAM-1; VLA-4