title: Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells.
abstract: Lung carcinoma is the leading cause of cancer-related death worldwide, and among this cancer, non-small cell lung carcinoma (NSCLC) comprises the majority of cases. Furthermore, recurrence and metastasis of NSCLC correlate well with CD133+ve tumor cells, a small population of tumor cells that have been designated as cancer stem cells (CSC). We have demonstrated for the first time high expression of D2dopamine (DA) receptors in CD133+ve adenocarcinoma NSCLC cells. Also, activation of D2DA receptors in these cells significantly inhibited their proliferation, clonogenic ability, and invasiveness by suppressing extracellular signal-regulated kinases 1/2 (ERK1/2) and AKT, as well as down-regulation of octamer-binding transcription factor 4 (Oct-4) expression and matrix metalloproteinase-9 (MMP-9) secretion by these cells. These results are of significance as D2DA agonists that are already in clinical use for treatment of other diseases may be useful in combination with conventional chemotherapy and radiotherapy for better management of NSCLC patients by targeting both tumor cells and stem cell compartments in the tumor mass.
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Soumyabrata
authors.initials: S
authors.lastname: Roy
authors.affiliation: the Department of Pathology, Ohio State University, Columbus, Ohio 43210.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: the Division of Virology, National Institute of Cholera and Enteric Diseases, Kolkata 700010, India.
authors.forename: Mukti Kant
authors.initials: MK
authors.lastname: Nayak
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Avishek
authors.initials: A
authors.lastname: Bhuniya
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Tithi
authors.initials: T
authors.lastname: Ghosh
authors.affiliation: the Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, Kolkata 700032, India, and.
authors.forename: Suman
authors.initials: S
authors.lastname: Kundu
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Sarbari
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
authors.affiliation: From the Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India, partha42002@yahoo.com.
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Dasgupta
authors.affiliation: the Department of Pathology, Ohio State University, Columbus, Ohio 43210, sujit.basu@osumc.edu.|the Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
mesh_terms: D000072283:A549 Cells; D000071916:AC133 Antigen; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*
chemical_list: D000071916:AC133 Antigen; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D017448:Receptors, Dopamine D2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: D2 receptors; cancer; cancer biology; cancer stem cells; cancer therapy; dopamine; lung cancer; signal transduction