Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets
Tessa Y.S. Le Large, … , Elisa Giovannetti, Maarten F. Bijlsma
Tessa Y.S. Le Large, … , Elisa Giovannetti, Maarten F. Bijlsma
Published July 7, 2020
Citation Information: JCI Insight. 2020;5(15):e138290. https://doi.org/10.1172/jci.insight.138290.
View: Text | PDF
Research Article Cell biology Oncology

Microdissected pancreatic cancer proteomes reveal tumor heterogeneity and therapeutic targets

  • Text
  • PDF
Abstract

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.

Authors

Tessa Y.S. Le Large, Giulia Mantini, Laura L. Meijer, Thang V. Pham, Niccola Funel, Nicole C.T. van Grieken, Bart Kok, Jaco Knol, Hanneke W.M. van Laarhoven, Sander R. Piersma, Connie R. Jimenez, G. Kazemier, Elisa Giovannetti, Maarten F. Bijlsma

×

Figure 1

Proteome analysis of PDAC samples.

Options: View larger image (or click on image) Download as PowerPoint
Proteome analysis of PDAC samples.
(A) Flowchart of the experimental set...
(A) Flowchart of the experimental set up of the proteome landscape analysis (n = 16 for the LCM analysis, n = 16 bulk tumor analysis). (B) Representative example images of 2 PDAC tumors during the LCM procedure. Slides show before and after tumor microdissection and after stroma microdissection. Original magnification, ×10. (C) Principle component analysis (PCA) of MS/MS data shows separation of the epithelial compartment from stroma (n = 16), tumor (n = 15), and bulk samples (n = 11). (D) Unsupervised hierarchical clustering of all proteins shows compartment-specific expression of all samples (n = 42). Heatmap colors indicate relative expression levels.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts