Proteomics

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Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors and Matched Spontaneous Distant Metastases


ABSTRACT: Metastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indicated by bioluminescence imaging (BLI), and matched subcutaneous primary tumors. Corresponding histology proved the human origin of metastatic lesions. Ovarian metastases were commonly larger than liver metastases indicating differential outgrowth capacities. Among ~1,700 proteins identified at each of the three sites, 89 proteins were differentially regulated in ovarian metastases while 290 proteins were regulated in liver metastases. There was an overlap of 26 and 10 proteins up- and down-regulated at both metastatic sites, respectively, most of which were so far not related to metastasis such as LYPLA2, ACTL8, EIF4B, LGALS7, GFAP, and ELAVL4. Moreover, we established in vitro sublines from primary tumor and metastases and demonstrate differences in cellular protrusions, migratory/invasive potential and glycosylation. Summarized, this work identified several novel putative drivers of metastasis formation that are tempting candidates for future functional studies.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Ovary, Liver, Neuroblastoma Cell

DISEASE(S): Neuroblastoma

SUBMITTER: Lorena Hänel  

LAB HEAD: Prof. Dr. Tobias Lange

PROVIDER: PXD009744 | Pride | 2018-09-24

REPOSITORIES: Pride

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Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors and Matched Spontaneous Distant Metastases.

Hänel Lorena L   Gosau Tobias T   Maar Hanna H   Valentiner Ursula U   Schumacher Udo U   Riecken Kristoffer K   Windhorst Sabine S   Hansen Nils-Owe NO   Heikaus Laura L   Wurlitzer Marcus M   Nolte Ingo I   Schlüter Hartmut H   Lange Tobias T  

Scientific reports 20180918 1


Metastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indi  ...[more]

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