title: A three-dimensional and temporo-spatial model to study invasiveness of cancer cells by heregulin and prostaglandin E2.
abstract: To study the temporal expression of motile structures and protease activity during colon cancer cell invasion by heregulin-beta1 (HRG) and prostaglandin E2 (PGE2), we have developed a three-dimensional spatial model system. HRG and PGE2 each induced the formation of well-organized, three-dimensional structures with empty spaces in the center and stimulated the expression of urokinase plasminogen activator (uPA) with differential localization of membrane-bound uPA at the focal adhesion points and leading edges of the motile cells. A specific cyclooxygenase-2 inhibitor blocked the formation of three-dimensional luminal glandular structures induced by HRG but did not block those induced by PGE2. A specific antagonist of uPA receptor completely blocked the formation of these luminal glandular structures induced by PGE2 and HRG. These findings suggest that HRG-mediated increased invasiveness of colon cancer cells is augmented at least in part by induction of PGE2 and uPA, and this augmentation may involve the formation of three-dimensional invasive structures via the uPA pathway. In addition, the three-dimensional model system presented here may have a wider application to screen the effects of therapeutic compounds and biomolecules on different spatial aspects of colonic biology, including cell growth, motility, invasion, survival, and apoptosis.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Adam
authors.forename: A
authors.initials: A
authors.lastname: Mazumdar
authors.forename: T
authors.initials: T
authors.lastname: Sharma
authors.forename: T R
authors.initials: TR
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Kumar
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D008858:Microscopy, Phase-Contrast; D009361:Neoplasm Invasiveness; D020890:Neuregulin-1 / Q000494:pharmacology* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D020890:Neuregulin-1; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone