title: Secretome protein signature of human gastrointestinal stromal tumor cells.
abstract: Strategies for correct diagnosis, treatment evaluation and recurrence prediction are important for the prognosis and mortality rates among cancer patients. In spite of major improvements in clinical management, gastrointestinal stromal tumors (GISTs) can still be deadly due to metastasis and recurrences, which confirms the unmet need of reliable follow-up modalities. Tumor-specific secreted, shed or leaked proteins (collectively known as secretome) are considered promising sources for biomarkers, and suitable for detection in biofluids. Herein, we stimulated cell secretion in the imatinib-sensitive GIST882 cell line and profiled the secretome, collected as conditioned media, by using a shotgun proteomics approach. We identified 764 proteins from all conditions combined, 51.3% being predicted as classically/non-classically secreted. The protein subsets found were dependent on the stimulatory condition. The significant increase in protein release by the classical pathway was strongly associated with markers already found in other cancer types. Furthermore, most of the released proteins were non-classically released and overlapped to a high degree with proteins of exosomal origin. Imatinib pre-treatment radically changed these secretory patterns, which can have clinical implications when investigating biomarkers in imatinib-treated versus non-treated GIST patients. Our results show, for the first time, that GISTs contain a secretome signature. In the search for suitable biomarkers in the more complex GIST patient samples, this study aids in the understanding of basic GIST secretome characteristics.
authors.affiliation: Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden. Electronic address: erik.berglund@ki.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Berglund
authors.affiliation: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Daré
authors.affiliation: Cancer Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rui M M
authors.initials: RM
authors.lastname: Branca
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, University Hospital, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Pinar
authors.initials: P
authors.lastname: Akcakaya
authors.affiliation: Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Fröbom
authors.affiliation: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, University Hospital, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, University Hospital, Cancer Center Karolinska, Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Zedenius
authors.affiliation: Cancer Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lukas
authors.initials: L
authors.lastname: Orre
authors.affiliation: Cancer Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: Lehtiö
authors.affiliation: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Bränström
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D011743:Pyrimidines / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D010879:Piperazines; D020543:Proteome; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Cell culture; Conditioned media; GIST; Proteomics; Sarcoma; Secretome