Role of CXCL12 and CXCR4 in tumor biology and metastasis

Ramesh K. Ganju, Yadwinder S. Deol, Mohd W. Nasser

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Chemokine receptor CXCR4 and its cognate ligand CXCL12, also known as stromal derived factor-1 (SDF-1), have been shown to play an important role in growth and metastasis of various tumors. CXCR4 is the most common chemokine receptor that has been demonstrated to be overexpressed in several cancers. Its overexpression is also correlated with poor clinical outcomes and survival in various cancers, including breast, prostate, and lung. CXCR4/CXCL12 signaling axis plays an important role in organ selective metastasis since CXCR4 overexpressing cancer cells have been shown to metastasize to organs such as bone, lymph nodes, liver, lung, and brain, which produce high amounts of CXCL12 and thus provide a favorable microenvironment. CXCR4/CXCL12 axis has been shown to enhance tumor growth and metastasis by maintaining cancer stem cells and modulating tumor stroma through activation of cancer-associated fibroblasts and recruitment of CXCR4+ endothelial precursor cells, thereby enhancing angiogenesis. CXCR4/CXCL12 axis has been shown to mediate both pro-tumorigenesis and metastasis by activating multiple signaling pathways, including protein tyrosine pathways through activation of Pyk2. Several CXCR4/CXCL12 antagonists/agonists have been shown to have potential therapeutic effects as they significantly inhibit tumor growth and metastasis of various cancers in both in vitro and in vivo mouse models. These studies suggest that the CXCR4/CXCL12 signaling axis is an important target for developing innovative therapies against various cancers.

Original languageEnglish (US)
Title of host publicationSignaling Pathways and Molecular Mediators in Metastasis
PublisherSpringer Netherlands
Pages221-243
Number of pages23
Volume9789400725584
ISBN (Electronic)9789400725584
ISBN (Print)9400725574, 9789400725577
DOIs
Publication statusPublished - Jan 1 2012

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ganju, R. K., Deol, Y. S., & Nasser, M. W. (2012). Role of CXCL12 and CXCR4 in tumor biology and metastasis. In Signaling Pathways and Molecular Mediators in Metastasis (Vol. 9789400725584, pp. 221-243). Springer Netherlands. https://doi.org/10.1007/978-94-007-2558-4_9