Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets.

Autor:	Le Large TY; Department of Surgery and.; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; Laboratory for Experimental Oncology and Radiobiology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Mantini G; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; Cancer Pharmacology Lab, Fondazione Pisana per la Scienza, Pisa, Italy., Meijer LL; Department of Surgery and.; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Pham TV; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Funel N; Unit of Anatomic Pathology II, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy., van Grieken NC; Unit of Anatomic Pathology II, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy., Kok B; Department of Surgery and., Knol J; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., van Laarhoven HW; Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Piersma SR; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Jimenez CR; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; OncoProteomics Laboratory, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Kazemier G; Department of Surgery and., Giovannetti E; Department of Medical Oncology, Amsterdam University Medical Centers, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; Cancer Pharmacology Lab, Fondazione Pisana per la Scienza, Pisa, Italy., Bijlsma MF; Laboratory for Experimental Oncology and Radiobiology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands.; Oncode Institute, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2020 Aug 06; Vol. 5 (15). Date of Electronic Publication: 2020 Aug 06.
DOI:	10.1172/jci.insight.138290
Abstrakt:	Pancreatic ductal adenocarcinoma (PDAC) is characterized by a relative paucity of cancer cells that are surrounded by an abundance of nontumor cells and extracellular matrix, known as stroma. The interaction between stroma and cancer cells contributes to poor outcome, but how proteins from these individual compartments drive aggressive tumor behavior is not known. Here, we report the proteomic analysis of laser-capture microdissected (LCM) PDAC samples. We isolated stroma, tumor, and bulk samples from a cohort with long- and short-term survivors. Compartment-specific proteins were measured by mass spectrometry, yielding what we believe to be the largest PDAC proteome landscape to date. These analyses revealed that, in bulk analysis, tumor-derived proteins were typically masked and that LCM was required to reveal biology and prognostic markers. We validated tumor CALB2 and stromal COL11A1 expression as compartment-specific prognostic markers. We identified and functionally addressed the contributions of the tumor cell receptor EPHA2 to tumor cell viability and motility, underscoring the value of compartment-specific protein analysis in PDAC.
Databáze:	MEDLINE
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