Matrix control of pancreatic cancer

New insights into fibronectin signaling

Mary Topalovski, Rolf A. Brekken

Research output: Contribution to journalArticle

27 Citations (Scopus)

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)
JournalCancer Letters
DOIs
StateAccepted/In press - 2015

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Pancreatic Neoplasms
Fibronectins
Adenocarcinoma
Neoplasms
Neoplasm Metastasis
Drug Therapy
Therapeutics
Growth
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Matrix control of pancreatic cancer : New insights into fibronectin signaling. / Topalovski, Mary; Brekken, Rolf A.

In: Cancer Letters, 2015.

Research output: Contribution to journalArticle

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