P-77 細胞の接着と増殖を促進するダンベル型小分子化合物アドヘサミンの発見と作用機序(ポスター発表の部)

抄録

Interactions between cell and extracellular matrix are pivotal survival of adherent cells both in vivo and in vitro. In vitro maintenance of adherent cells can be promoted by coating culture plates with artifical substrates, including native extracellular matrix molecules derived from either human/animal tissues or recombinant bacteria. However, many of these native molecules are not chemically defined and have the risk of contamination. Chemically defined synthetic polycationic peptides, such as poly(L/D-lysine), are also widely used for coating cell culture dises. Such nonspecific adhesive coatings, however, may cause abnormal cell-spreading, leading to cytotoxoc or physiologically irrelevant outcome. S synthetic molecule that promotes physiological cell adhesion would serve as a convenient reagent for a reproducible, safe, and biocompatible cell culture. In this paper, we report the discovery of the first non-peptidic organic molecule whose simple addition induces apparently normal cell adhesion to culture plates. Chemical and cell biological experiments suggest that adhesamine is most likely to exert its cell-adhesion activity by interacting with selective sulfated glysosaminoglycans (GAGs) to modulate cell surfate properties and intercellular signaling pathways. It is unllikely that adhesamine simply alters physical properties of cell surface through electrostatic interactions. Unlike poly-L-lysine, adhesamine induces apparently normal cell adhesion accompanied with organized actin structures, focal adhesion, activation of focal adhesion kinase/ERK kinases. Non-peptidic, completely organic molecules that promote normal cell adhesion and growth have never been reported, to our knowledge. Adhesamine may provide an additional framework to complement existing naturally derived or peptidic materials.