Tumorigenic properties of alternative osteopontin isoforms in mesothelioma.
Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.
Ivanov
Sergey V
SV
Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016, USA. Sergey.Ivanov@med.nyu.edu
Ivanova
Alla V
AV
Goparaju
Chandra M V
CM
Chen
Yuanbin
Y
Beck
Amanda
A
Pass
Harvey I
HI
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D053495:Osteopontin / Q000235:genetics / Q000502:physiology*; D010994:Pleura / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D054363:Solitary Fibrous Tumor, Pleural / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin