title: Specific expression of OATPs in primary small cell lung cancer (SCLC) cells as novel biomarkers for diagnosis and therapy.
abstract: The expression of organic anion transporting polypeptides (OATPs) was elucidated in cell lines from small cell lung cancer (SCLC) and lung carcinoids and in paraffin-embedded samples from primary and metastatic SCLCs. We found a strong relationship between OATP expression and the origin of the cells, as cells from primary or metastatic SCLC and carcinoid tumors differ with respect to OATP levels. OATP4A1 is most prominent in non-malignant lung tissue and in all SCLC and carcinoid cell lines and tissues, OATP5A1 is most prominent in metastatic cells, and OATP6A1 is most prominent in SCLC cell lines and tumors. Treatment with topotecan, etoposide and cisplatin caused significant changes in the expression patterns of OATP4A1, OATP5A1, OATP6A1, chromogranin and synaptophysin. This effect was also evident in GLC-14 cells from an untreated SCLC patient before chemotherapy compared to GLC-16/-19 chemoresistant tumor cells from this patient after therapy. mRNA expression of OATP4A1, 5A1 and 6A1 correlates with protein expression as confirmed by quantitative microscopic image analysis and Western blots. OATPs might be novel biomarkers for tumor progression and the development of metastasis in SCLC patients.
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brenner
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Cluster for Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Klameth
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Juliane
authors.initials: J
authors.lastname: Riha
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Schölm
authors.affiliation: Cluster for Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Bajna
authors.affiliation: Department of Surgery, Donauspital, Vienna, Austria; Cluster for Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ausch
authors.affiliation: Cluster for Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria; Department of Pathology, Donauspital, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Reiner
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. Electronic address: theresia.thalhammer@meduniwien.ac.at.
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
authors.affiliation: Cluster for Translational Oncology, Ludwig Boltzmann Society, Vienna, Austria; Department of Internal Medicine 2, Donauspital, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Buxhofer-Ausch
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D019772:Topotecan / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C569014:SYP protein, human; D016708:Synaptophysin; D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin
keywords: Chemotherapy; Neurogenic marker; OATP gene expression; Organic anion transporting polypeptide (OATP); Small cell lung cancer (SCLC)