Therapeutic differentiation of tumor-derived insulin-producing cells selected for resistance to diabetogenic drugs.
Differentiation therapy has been proposed as a new approach to selectively engage the process of tumor cell differentiation during chemotherapy of cancer. Our recent in vitro study suggests that such an approach can be extended and utilized for the selection of tumor-derived insulin-producing cells for transplantation. Repeated treatment with streptozotocin selected toxin resistant subpopulation of insulin producing tumor RINmS cells, characterized by increased level of insulin content and secretion. In the present study RINmS cells were found to have higher glucose sensitivity and insulin response compared with parental RINm cells. In addition, compounds known to induce elevated level of cAMP in beta-cells, such as isobutyl methyl xanthine, and forskolin, potentiated glucose-induced insulin secretion of RINmS, but had no effect on the naive parental RINm cells. These experiments suggest that differentiation therapy can be utilized for engineering insulin producing cells with improved defense and secretory mechanisms.
Bloch
K
K
Felsenstein Medical Research Center, Tel-Aviv University, Petah Tikva, Israel.
Vardi
P
P
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004351:Drug Resistance; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D010190:Pancreatic Neoplasms; D051381:Rats; D013311:Streptozocin / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D007328:Insulin; D005576:Colforsin; D013311:Streptozocin; D000242:Cyclic AMP; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine