Targeting endoglin expressing cells in the tumor microenvironment does not inhibit tumor growth in a pancreatic cancer mouse model

Mark J. A. Schoonderwoerd, Sarah K. Hakuno, Martijn Sassen, Eleonore B. Kuhlemaijer, Madelon Paauwe, Marije Slingerland, Marieke F. Fransen, Lukas J. AC Hawinkels

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5 Citations (Scopus)


Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer and is known to have low immunogenicity and an immunosuppressive microenviron-ment. It is also characterized by high accumulation of dense stroma, composed of mostly cancer-associated fibroblasts (CAFs). Multiple subsets of CAFs are described, with one of them expressing the transforming growth factor (TGF)-β co-receptor endoglin. In previous work, we and others have shown that endoglin-expressing CAFs stimulate tumor progression and metastasis. Therefore, in this study, we set out to investigate the role of endoglin-expressing CAFs in pancreatic cancer progression. Methods: First, we investigated the expression of endoglin on CAFs in both human tissues as well as a mouse model for PDAC. Since CAF-specific endoglin expression was high, we targeted endoglin by using the endoglin neutralizing antibody TRC105 in the murine KPC model for PDAC. Results: Although some signs of immune activation were observed, TRC105 did not affect tumor growth. Since 90% of the CD8+ T-cells expressed the immune checkpoint PD-1, we investigated the combination with a PD1 checkpoint inhibitor, which did not enhance therapeutic responses. Finally, genetic deletion of endoglin from collagen 1a1 expressing cells also did not affect the growth of the mouse KPC tumors. Conclusion: Our results show that although endoglin is highly expressed on PDAC-CAFs and signaling is efficiently inhibited by TRC105, this does not result in decreased tumor growth in the KPC model for pancreatic cancer.
Original languageEnglish
Pages (from-to)5205-5220
Number of pages16
JournalOncoTargets and Therapy
Publication statusPublished - 2021


  • Cancer-associated fibroblasts
  • Endoglin
  • KPC
  • PDAC
  • Stroma
  • TRC105

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