Retinoic acid improves a hybridoma culture in a fructose-based medium by up-regulation of fructose incorporation via retinoid nuclear receptors.
Fructose was focused on as an alternative sugar source to glucose in a hybridoma culture medium because it decreases lactate production during cultivation, leading to cell and product stability. But, not all human hybridoma cell lines grew well in a fructose-based serum-free medium. We found that the addition of all-trans-retinoic acid to the fructose-based medium improved the growth and monoclonal antibody production of hybridoma cell lines by up-regulation of fructose incorporation that represented increased expression of the fructose transporter, GLUT5. Selective activation of retinoid nuclear receptor by synthetic ligands showed that both retinoic acid receptors and retinoid X receptors might be related to the improvement of the fructose-based hybridoma culture. This study might be applicable to cell cultures susceptible to lactate and pH changes as well as hybridoma cultures.
Inoue
Yuichi
Y
Faculty of Agriculture, Kagoshima University, Kagoshima, Japan. inoue@kct.ac.jp
Kawahara
Hiroharu
H
Shirahata
Sanetaka
S
Sugimoto
Yasushi
Y
D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000917:Antibody Formation / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D005632:Fructose / Q000378:metabolism*; D051296:Glucose Transporter Type 5 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019344:Lactic Acid / Q000096:biosynthesis; D008726:Methoprene / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D001565:Benzoates; D003470:Culture Media; D051296:Glucose Transporter Type 5; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; C495726:SLC2A5 protein, human; D013764:Tetrahydronaphthalenes; C068073:Am 580; D005632:Fructose; D019344:Lactic Acid; D014212:Tretinoin; D012313:RNA; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D008726:Methoprene