Editorial [Hot topic: Cell Adhesion Molecules: Structure, Function, Drug Design, and Biomaterials (Executive Editor: Seetharama D. Satyanarayanajois)]

Cell adhesion molecules are critical components of communication among cells. They mediate the contact between cells as well as between cells and the extracellular matrix, thus maintaining the integrity of the tissues. A majority of adhesion molecules can be grouped into integrins, cadherins, selectins, and immunoglobulin superfamilies. Adhesion molecules participate in many stages of immune response; they regulate leukocyte circulation, the homing of lymphoid cells to tissues and inflammatory sites, migration across endothelial cells, and T-cell stimulation. During T-cell immune response, adhesion molecules form a specialized junction between the T cell and the antigen-presenting cell. Adhesion molecules also play a major role in cell proliferation and differentiation, making them important in cancer development. Thus, many researchers (academic/pharmaceutical) have focused their attention on targeting adhesion molecules for developing therapeutic agents. Most of these efforts are intended to develop drugs for autoimmune diseases, inflammatory diseases and cancer. In recent years there has been an attempt to use the “adhesion properties” of these molecules for making biocompatible materials and for drug delivery. In this issue of Current Pharmaceutical Design, we are presenting eight review articles on adhesion molecules written by experts in this area. These articles provide insight into the basic mechanisms of protein-protein interactions at the cell surface, ligands that were designed for drug targeting, and cell adhesion molecules as biomaterials. The topics covered are at the interface of biotechnology, structural biology, and medicinal chemistry. Hence, they should be of great interest to biologists, clinicians, and pharmaceutical scientists. Integrins form a family of adhesion receptors that mediate cell-cell and cell-extracellular matrix interactions. Leukocyte function-associated antigen-1 (LFA-1) is an integrin molecule that is expressed on the surface of all leukocytes and is critical for their antigen-specific responses and homing. The natural ligands of LFA-1 are ICAMs (intercellular adhesion molecules), of which ICAM-1 is the most important. In the first article, Zimmerman and Blanco [1] discuss the structurally diverse collection of small molecule inhibitors that are characterized and developed either to bind to the αL I-domain or to the β2 I-like domain. A summary of the structure and regulation of LFA-1 is given, followed by a description of the different classes of inhibitors that have been described to date. Apart from their role in cell adhesion, integrins have also been shown to be important in mediating cell survival, proliferation, differentiation, and migration. Lu and coworkers [2] discuss the potential role of integrins in atherosclerosis and also address the reasons that integrins present attractive targets for drug design for chemotherapy and for cardiovascular diseases. Biological obstacles, such as intestinal mucosa and the blood-brain barrier, protect the systemic circulation from pathogens. Adhesion molecules are key components of these barriers that act to keep them as tight junctions. Cadherins form the main component of the barriers, called adherens, and have important implications in cancer metastasis. While these molecules protect the important tissues in the body, they also pose a problem for delivering the drug into the systemic circulation. In the third article in this issue, Al Moustafa et al. [3] focus on the interaction between human papilloma viruses (HR-HPV), human epidermal growth factor receptor-2 (ErbB2), and the E-cadherin/catenin complex in human carcinomas, including cervical, colorectal, head and neck, and breast cancers. In another article, Syrigos and coworkers review the existing data on the implications of adhesion molecules, cadherins, and integrins in the pathogenesis of lung cancer, as well as the application of certain adhesion molecules as potential surrogate markers in lung cancer patients [4]. Adhesion molecules help to keep a group of cells together in multicellular organisms by the interaction between cells and the extracellular matrix. Understanding the interaction between cells and extracellular matrix has been useful in designing biomaterials and fabricating nanomaterials that can deliver drugs across the blood-brain and other barriers. Articles by Venugopal et al. [5], Kim and Ku [6], and Choudhary [7] discuss the technologies that may be useful for drug delivery, creating biomaterials including dental implants, and using adhesion molecules. Vasculogenesis and angiogenesis play critical roles in the ability of tumors to grow, invade locally, and metastasize from the primary tumor site. In a variety of malignancies, vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (ICAM), and E-selectin seem to appear in elevated levels compared to normal tissues. In the last article of this issue, Papaetis et al. [8] have reviewed the importance of VEGF and other proteins in renal cell cancer (RCC) and existing targeted therapies for RCC, and present, recent clinical data. There is no doubt that researchers in the areas related to adhesion molecules have come a long way since starting with only an interest in immunology nearly twenty years ago. The drug candidates targeted to adhesion molecules described in this issue represent novel compounds designed to treat several chronic diseases. We believe that the articles presented in this issue provide a summary of the state-of-the-art drug design and technology available using adhesion molecules. These articles also highlight the fact that research on adhesion molecules spans several key disciplines, including medicinal chemistry, structural biology, and bionanotechnology.