Amplification of invasiveness in organotypic cultures after NBT-II rat bladder carcinoma stimulation with in vitro scattering factors.
Acidic fibroblast growth factor (aFGF) or transforming growth factor-alpha (TGF-alpha), in addition to being mitogenic, induce individual scattering of NBT-II rat bladder carcinoma cell clusters on tissue culture dishes, suggesting that they may contribute to tumor cell dissemination. To assay their scattering potential and their effect on cell invasiveness in a more complex and physiologically relevant model, we analyzed the behavior of NBT-II spheroids confronted with urinary bladder in organotypic cultures. NBT-II spheroids progressively replaced the urothelium at the site of contact with the bladder explant. In the absence of aFGF or TGF-alpha, inserted cells grew in a pattern suggestive of local hyperplasia, with occasional invasive cell protrusions. Exogenous scattering growth factors elicited a more rapid appearance of these protrusions, which were also more numerous. NBT-II cells transfected with cDNA constructs bearing the gene of aFGF, TGF-alpha or the oncogene hst/KFGF were also used. After exogenous or autocrine stimulation of NBT-II cells with the growth factors, a deeper penetration of the bladder wall in the form of nodular outgrowths and clusters of infiltrating cells was always observed. Altogether these observations suggest that the stimulation of NBT-II clusters by scattering/growth factors can promote cell shedding and amplify invasiveness in the complex extracellular environment of bladder tissues.
Tucker
G C
GC
Laboratoire de Physiopathologie du Développement, URA 1337, CNRS Ecole Normale Supérieure, Paris, France.
Delouvée
A
A
Jouanneau
J
J
Gavrilovic
J
J
Moens
G
G
Vallés
A M
AM
Thiery
J P
JP
D000818:Animals; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression / Q000235:genetics; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009924:Organ Culture Techniques; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001743:Urinary Bladder / Q000033:anatomy & histology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D006133:Growth Substances; D016211:Transforming Growth Factor alpha; D016220:Fibroblast Growth Factor 1