Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy

Richard L. Sleightholm, Beth K. Neilsen, Jing Li, Maria M. Steele, Rakesh K Singh, Michael A Hollingsworth, David Oupicky

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression. This receptor, in conjunction with its primary chemokine ligand CXCL12, promotes pancreatic cancer development, invasion, and metastasis through the management of the tumor microenvironment via complex crosstalk with other pathways. Thus, CXCR4 likely contributes to the poor prognoses observed in patients afflicted with this malignancy. Recent exploration of combination therapies with CXCR4 antagonists have demonstrated improved outcomes, and abolishing the contribution of this pathway may prove crucial to effectively treat pancreatic cancer at both the primary tumor and metastases.

Original languageEnglish (US)
Pages (from-to)158-170
Number of pages13
JournalPharmacology and Therapeutics
Volume179
DOIs
StatePublished - Nov 2017

Fingerprint

Pancreatic Neoplasms
Neoplasms
Tumor Microenvironment
Neoplasm Metastasis
Chemokines
Therapeutics
Physiological Phenomena
Chemokine CXCL12
Chemokine Receptors
Stromal Cells
Ligands
Growth

Keywords

  • CXCR4
  • Cancer therapy
  • Molecular mechanism
  • Pancreatic cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy. / Sleightholm, Richard L.; Neilsen, Beth K.; Li, Jing; Steele, Maria M.; Singh, Rakesh K; Hollingsworth, Michael A; Oupicky, David.

In: Pharmacology and Therapeutics, Vol. 179, 11.2017, p. 158-170.

Research output: Contribution to journalReview article

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AU - Singh, Rakesh K

AU - Hollingsworth, Michael A

AU - Oupicky, David

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AB - Chemokine networks regulate a variety of cellular, physiological, and immune processes. These normal functions can become appropriated by cancer cells to facilitate a more hospitable niche for aberrant cells by enhancing growth, proliferation, and metastasis. This is especially true in pancreatic cancer, where chemokine signaling is a vital component in the development of the supportive tumor microenvironment and the signaling between the cancer cells and surrounding stromal cells. Although expression patterns vary among cancer types, the chemokine receptor CXCR4 has been implicated in nearly every major malignancy and plays a prominent role in pancreatic cancer development and progression. This receptor, in conjunction with its primary chemokine ligand CXCL12, promotes pancreatic cancer development, invasion, and metastasis through the management of the tumor microenvironment via complex crosstalk with other pathways. Thus, CXCR4 likely contributes to the poor prognoses observed in patients afflicted with this malignancy. Recent exploration of combination therapies with CXCR4 antagonists have demonstrated improved outcomes, and abolishing the contribution of this pathway may prove crucial to effectively treat pancreatic cancer at both the primary tumor and metastases.

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