Intercellular adhesion disorders in tumorigenesis

The review discusses the problem of adhesion impairment in the course of tumorigenesis and aging. We hypothesize that impairment of homophilic intercellular adhesion in the target tissue results in developing conditions, which are favorable for malignancy, invasion, and metastases. Like a phoenix vanishing during the initiation of a primary tumor by breaking contacts between identical cells, adhesion molecules reappear with a new quality (the phoenix rising mechanism), thereby causing invasive and metastatic behavior of tumor cells. Due to this, primary tumor cells acquire motility and the ability to form metastases, which are the cause of most cancer deaths. At the same time, the provision of adhesive bonds between cancer cells and immune effector cells can also be controlled by one of the main neurotransmitters, dopamine (DA). The discovery of peripheral DA in lymphocytes gave grounds to the assumption that DA is involved in the infiltration of tumor leukocytes. DA receptors are found on cells of the adaptive (specific) immune response: T and B lymphocytes. Direct communication between brain DA and peripheral DA is crucial in modulating immune function. Peripheral DA mediates differentiation, binding to tumor cells, and cytotoxicity of CD8+ T cells. The review also confirms the need for the development of adhesion pharmaceutical agents. The disruption of intercellular adhesion in the target tissue and the general deficiency of immune surveillance can be controlled by central mechanisms involving brain DA, which is capable of regulating the active phase of immune responses against the tumor by means of adhesive interactions in the immune system, interfering with the process and thereby interrupting the development of a malignant neoplasm initiated by a local mutation in the tissue. The concept reveals the stress mechanism of cancer etiology and creates prospects for new methods of diagnostics, prevention and treatment of tumors, which can become another step towards solving the problem of malignant neoplasms.