45T-1, an established cell line with characteristics of Sertoli cells, forms organized aggregates in vitro after exposure to tumor necrosis factor alpha
K. Szalay et al., 45T-1, an established cell line with characteristics of Sertoli cells, forms organized aggregates in vitro after exposure to tumor necrosis factor alpha, EUR J CELL, 78(5), 1999, pp. 331-338
In the testis TNF is produced by germinal cells, The putative role of tumor
necrosis factor alpha (TNF) in development and differentiation was investi
gated in 45T-1 mouse cell cultures, a cell line with characteristic markers
of Sertoli cells, established from transgenic mouse families expressing th
e polyoma large T antigen in their testes. Exposure to TNF elicited a gradu
al assembly of the cells of the monolayer into highly organized spheroids.
The first morphological sign of the changes was detected one week after TNF
treatment by anti-desmin immunostaining which showed the formation of foci
in the culture consisting of several hundred cells connected by an increas
ing number of cell contacts, Between days 10-20 the cells formed large ovoi
d or vermiform aggregates covered by several layers of flat, elongated cell
s. These cells extended septae into the inner mass of the spheroids consist
ing of loosely arranged, large polygonal or palisadic cells. The spheroids
were surrounded by radially arranged elongated cells covered by small blebs
, TNF treatment upregulated laminin expression in 45T-1 cell cultures, whic
h is known to induce formation of cord-like structures by Sertoli cells in
vitro. Coculturing 45T-1 cells with immortalized germinal cells or TNF-prod
ucing HeLa cells also lead to the formation of spheroids, These observation
s suggest that TNF production of germinal cells might contribute to the org
anization/differentiation of Sertoli cells.