Matrix control of pancreatic cancer: New insights into fibronectin signaling

Mary Topalovski, Rolf A. Brekken

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease that resists most current therapies. A defining characteristic of PDA is an intense fibrotic response that promotes tumor cell invasion and chemoresistance. Efforts to understand the complex relationship between the tumor and its extracellular network and to therapeutically perturb tumor–stroma interactions are ongoing. Fibronectin (FN), a provisional matrix protein abundant in PDA stroma but not normal tissues, supports metastatic spread and chemoresistance of this deadly disease. FN also supports angiogenesis, which is required for even hypovascular tumors such as PDA to develop and progress. Targeting components of the tumor stroma, such as FN, can effectively reduce tumor growth and spread while also enhancing delivery of chemotherapy. Here, we review the molecular mechanisms by which FN drives angiogenesis, metastasis and chemoresistance in PDA. In light of these new findings, we also discuss therapeutic strategies to inhibit FN signaling.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalCancer Letters
Volume381
Issue number1
DOIs
StatePublished - Oct 10 2016

Keywords

  • Chemoresistance
  • Extracellular matrix
  • Fibronectin
  • Integrin
  • Metastasis
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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