2. Academic Validation
  3. CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ

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

  • Cancer Res. 2015 Dec 15;75(24):5283-98. doi: 10.1158/0008-5472.CAN-15-2282-T.
Hangyi H Yan 1,  Jian Jiang 2,  Yanli Pang 3,  B R Achyut 1,  Michael Lizardo 4,  Xinhua Liang 5,  Kent Hunter 1,  Chand Khanna 4,  Christine Hollander 1,  Li Yang 6
Affiliations

Affiliations

  • 1 Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
  • 2 Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China.
  • 3 Department of Physiology & Pathophysiology, Peking University Health Science Center, Beijing, P.R. China.
  • 4 Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland.
  • 5 State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China.
  • 6 Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. yangl3@mail.nih.gov.
PMID: 26483204 DOI: 10.1158/0008-5472.CAN-15-2282-T
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.

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