title: Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.
abstract: Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication.
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation; victoria.shender@gmail.com.
authors.forename: Victoria O
authors.initials: VO
authors.lastname: Shender
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation;
authors.forename: Marat S
authors.initials: MS
authors.lastname: Pavlyukov
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation;
authors.forename: Rustam H
authors.initials: RH
authors.lastname: Ziganshin
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation; ‖Moscow Institute of Physics and Technology, Institutskiy pereulok 9, Dolgoprudny 141700, Russian Federation;
authors.forename: Georgij P
authors.initials: GP
authors.lastname: Arapidi
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation;
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Kovalchuk
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation;
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Anikanov
authors.affiliation: ‖Moscow Institute of Physics and Technology, Institutskiy pereulok 9, Dolgoprudny 141700, Russian Federation; **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation;
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Altukhov
authors.affiliation: ‖Moscow Institute of Physics and Technology, Institutskiy pereulok 9, Dolgoprudny 141700, Russian Federation; **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation;
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Alexeev
authors.affiliation: **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation;
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Butenko
authors.affiliation: ‡‡Research Resource Center molecular and Cell Technologies, Saint-Petersburg State University, Universitetskaya nab. 7-9, Saint-Petersburg 199034, Russian Federation; §§Analytical Phytochemistry Laboratory, Komarov Botanical Institute, Prof. Popov Street 2, Saint-Petersburg 197376, Russia;
authors.forename: Alexey L
authors.initials: AL
authors.lastname: Shavarda
authors.affiliation: **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation;
authors.forename: Elena B
authors.initials: EB
authors.lastname: Khomyakova
authors.affiliation: ¶¶Faculty of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russian Federation;
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Evtushenko
authors.affiliation: ‖‖Russian Scientific Center of Roentgenoradiology, Profsoyuznaya str. 86, Moscow 117997, Russian Federation;
authors.forename: Lev A
authors.initials: LA
authors.lastname: Ashrafyan
authors.affiliation: ‖‖Russian Scientific Center of Roentgenoradiology, Profsoyuznaya str. 86, Moscow 117997, Russian Federation;
authors.forename: Irina B
authors.initials: IB
authors.lastname: Antonova
authors.affiliation: ‖‖Russian Scientific Center of Roentgenoradiology, Profsoyuznaya str. 86, Moscow 117997, Russian Federation;
authors.forename: Igor N
authors.initials: IN
authors.lastname: Kuznetcov
authors.affiliation: **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation;
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Gorbachev
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation;
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Shakhparonov
authors.affiliation: From the ‡Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya str. 16/10, Moscow 117997, Russian Federation; **Research Institute of Physical Chemical Medicine, Malaya Pirogovskaya str., 1a, Moscow 119435, Russian Federation; Kazan Federal University, Kremlyovskaya str. 18, Kazan 420008, Russian Federation.
authors.forename: Vadim M
authors.initials: VM
authors.lastname: Govorun
mesh_terms: D017398:Alternative Splicing; D001201:Ascites / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication; D045744:Cell Line, Tumor; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055442:Metabolome / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D017381:Spliceosomes / Q000737:chemistry / Q000378:metabolism; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome; D012334:RNA, Neoplasm