engleski

Morfing into Teratoma: The Inhibition Role of Developmental Signal Molecules Retinoic Acid and Neural Growth Factor

Previously, we have explored molecular features of retinoids in a selected X-category drugs (including retinoic acid (RA)) and found that predicted ADMET Risk scores are 4, CYP Risk 0, TOX Risk 2. RA and neural growth factor (NGF) are essential for proper embryonal development of human and vertebrate embryos. Both agents affect same types of cancer cells too. Embryo-derived teratomas are instructive tumor model for elucidation impact of RA and NGF on both tumor and embryonal cels. Before, we have found that both agents inhibited differentiation of some tissues in cultivated teratomas derived from gastrulating mammalian embryos (critical stage of development). Therefore, our purpose was trying to create one tissue altering differentiation with RA/NGF combination. A unique organ culture system was used for cultivation of embryo-derived rat teratomas at the air-liquid interface during two weeks, using Eagle's MEM with 50% of homologous serum (control). NGF (100 ng/mL) or RA (10-5 mol/L) or both agents together were added in culture medium in the time frame of 9 days. Growth rate of teratomas was evaluated measuring average size using an eyepiece micrometer, and the changes of growth rate were expressed in percents. NGF impaired growth, while RA and RA/NGF-treated teratomas grow similar as control ones. The combination of RA/NGF acted on three different manner on differentiation process: conversion (epithelial metaplasia), stimulation (neural tissue, 100%) and inhibition (cartilage, gland epithelium, keratinization). These preliminary results showed, that it is possible using developmental signal molecules in different combination produced tissue which we want from mammalian embryo.

Embryo-derived teratomas; Retinoic Acid; Neural Growth Factor; Tissue differentiation

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