Open AccessTHE ROLE OF ALPHA-FETOPROTEIN RECEPTOR IN THE DELIVERY OF TARGETED PREPARATIONS IN ONCOLOGY
Author(s) -
H. M. Treshalina,
G. P. Smirnova,
С А Цуркан,
J. R Tcherkassova,
N. A. Lesnaya
Publication year - 2017
Publication title -
rossijskij onkologičeskij žurnal
Language(s) - English
Resource type - Journals
eISSN - 2412-9119
pISSN - 1028-9984
DOI - 10.18821/1028-9984-2017-22-1-4-14
Subject(s) - receptor , alpha fetoprotein , internalization , cancer research , biology , cancer , endocytosis , cell , cell type , cell culture , microbiology and biotechnology , medicine , biochemistry , genetics , hepatocellular carcinoma
There was executed the analysis of thematic literature during from 1956 to 2015 devoted to receptors to fetal proteins, including to alpha-fetoprotein (AFP) known in medicine as oncomarker and used by malignant cells for the organization of tumoral homeostasis. As protein carrier, AFP similar to albumin takes of vitally important molecules in a space «hydrophobic pocket» and moves inside a cell, but as the cancer-embryonal antigen (CEA) - determines the existence of a malignant tumor, but not the type of a neoplasm. On the bounding of AFP with teratogen and their internalization and delivery in an embryo there is based the development of ways of «address» delivery of substances into a cell. This is realized by means of receptor mediated endocytosis via specific membranous receptors to AFP (ReCAF) with high selectivity concerning malignant cells of various genesis. Up to 90% of all malignant cells of the human and tumor models for human and mammalians express AFP receptors, including rather recently opened stem tumor cells - the most probable source of metastasing. AFP production and expression of receptors is selectively raised in malignant tumors of patients and human tumor models. The hyperproduction of AFP and hyperexpression of ReCAF are related to the histologic type of tumor model and are characteristic for embrional cell tumors and hepatoblastomas with initially low drug sensitivity or with the resistance. When choosing the model it is necessary to consider that in different types of tumor cells ReCAF have specific features in cultivation which are not pronounced in conditions of an animal organism. More differentiated tumors are characterized by the larger level of the AFP production and a hyperexpression of ReCAF. The use of subcutaneous tumor xenografts signal for AFP localizations with the hyperexpression of receptors, allows to reveal mostly evidentially the effectiveness of the therapeutic system at the preclinical level. Address delivery of therapeutic systems created on the basis of AFP or its fragments is capable of causing the change of their pharmacological properties. The therapeutic prize is possible due to the induction of process of apoptosis via the mitochondrial pathway, but at the same time the fall in the cytotoxic capacity of system is possible.