Apoptosis in a tissue-like culture model of human colorectal adenoma cells.
Tissue-like cultures of LT97 human colonic adenoma cells were produced by plating on reconstructed connective tissue supports (CTR) containing colon-associated fibroblasts to form mucosal monolayers and polyp-like structures closely resembling the in vivo situation. Tight cell-cell contacts and a high density of desmosomes were observed in 93.8+/-3.5% of the section area for CTR cultures, but only in 17.8+/-10.0% of the area for cultures on collagen gels (CG) without fibroblasts. While LT97 cultures on plastic shed apoptotic bodies into the medium, they collected at the basal pole of the cell layer in the CTR cultures as is also observed in adenoma tissue. Only a small proportion was released into the medium as shown by the detection of apoptosis specific keratin fragments, which could be increased by 100microM of quercetin and resveratrol. In addition, tissue-like structures altered the relative effectivity of test compounds. As the tissue-like conditions closely resemble the situation in vivo tissue-like cultures are an important step towards the establishment of tissue reconstructs that can replace animal models in the analysis of basic mechanisms of growth control and the testing of tumor promoting and chemopreventive compounds and may even be superior in terms of predictivity as they use human cells.
Leuhuber
Katharina
K
Institution of Cell Imaging and Ultrastructure Research University of Vienna, Austria.
Klepal
Waltraud
W
Hausott
Barbara
B
Marian
Brigitte
B
D000236:Adenoma / Q000378:metabolism* / Q000648:ultrastructure; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D003094:Collagen; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D004353:Drug Evaluation, Preclinical; D008954:Models, Biological; D011794:Quercetin / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D003094:Collagen; D011794:Quercetin; D000077185:Resveratrol