CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ

Hangyi H Yan, Jian Jiang, Yanli Pang, B R Achyut, Michael Lizardo, Xinhua Liang, Kent Hunter, Chand Khanna, Christine Hollander, Li Yang

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1(+)CD11b(+) immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. Importantly, CCL9 overexpression in myeloid cells lacking TGFβ signaling rescued the tumor metastasis defect observed in mice with myeloid-specific Tgfbr2 deletion. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. In addition, targeting CCL9 may avoid the adverse effects of TGFβ-targeted therapy.

Original languageEnglish (US)
Pages (from-to)5283-98
Number of pages16
JournalCancer Research
Volume75
Issue number24
DOIs
StatePublished - Dec 15 2015
Externally publishedYes

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Keywords

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival
  • Chemokines, CC
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • In Situ Nick-End Labeling
  • Macrophage Inflammatory Proteins
  • Mice
  • Myeloid Cells
  • Neoplasm Invasiveness
  • Neoplasms, Experimental
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transfection
  • Transforming Growth Factor beta
  • Tumor Microenvironment
  • Journal Article
  • Research Support, N.I.H., Intramural

Cite this

Yan, H. H., Jiang, J., Pang, Y., Achyut, B. R., Lizardo, M., Liang, X., Hunter, K., Khanna, C., Hollander, C., & Yang, L. (2015). CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ. Cancer Research, 75(24), 5283-98. https://doi.org/10.1158/0008-5472.CAN-15-2282-T