ADHESION CONCEPT IN CANCER BIOLOGY: LOCAL AND CENTRAL MECHANISMS (PART 1)

Abstract

The review presents the concept the key mechanism of the tumor process is a violation of adhesion interactions involving local and central mechanisms. Local features of adhesive dysregulation are demonstrated in the first part. The lack of histospecific adhesion molecules expression resulting from stress or genetic mutation damages an important mechanism of antitumor protection of the tissue disrupting the processes of proliferation and differentiation. The deficiency of histone-specific homotypic adhesion molecules which occurs later exacerbates the disorders. This leads to a decrease in the expression of leukocyte integrins (LFA-1, Mac-1) ligands of the β2 family on the surface of immune effectors and to an increase also in the expression of adhesion molecules to the substrate-antigens VLA (very late activation) family of β1 -integrins on tumor cells. The first restricts the interaction of ICAM family molecules with their contra-receptors from the β2 -integrin family reducing the elimination of target cells by immune effectors which contributes to the screening of the tumor from antitumor surveillance. The second promotes the invasion of the tumor into the surrounding tissues, the formation of blood vessels as well as its heterotypic adhesion with other tissues which further stimulates the proliferation and suppression processes of tumor cells apoptosis. So, the adhesion molecules can be compared to the Phoenix bird: disappearing at the beginning of the process (between the similar cells), they reappear in a new quality (increasing adhesion to cells of other tissues), increasing the totalysm of the tumor. It should be taken into account that tumor cells due to adhesion dysregulation “isolate themselves from society”, lose their differentiation, their maturity and “fall into childhood”, being unable to perform specific, “adult” functions. So, cancer can be considered as a manifestation of the cells aging. Therefore, the anti-stress, endogenous geroprotective mechanisms activation based on the adhesion correction can be effective for preventing and treatment the oncological process.