Contribution of very late antigen-4 (VLA-4) integrin to cancer progression and metastasis

Martin Schlesinger, Gerd Bendas

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.