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Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis.

Publication ,  Journal Article
Chen, HJ; Edwards, R; Tucci, S; Bu, P; Milsom, J; Lee, S; Edelmann, W; Gümüs, ZH; Shen, X; Lipkin, S
Published in: J Clin Invest
September 2012

Chemotactic cytokines (chemokines) can help regulate tumor cell invasion and metastasis. Here, we show that chemokine 25 (CCL25) and its cognate receptor chemokine receptor 9 (CCR9) inhibit colorectal cancer (CRC) invasion and metastasis. We found that CCR9 protein expression levels were highest in colon adenomas and progressively decreased in invasive and metastatic CRCs. CCR9 was expressed in both primary tumor cell cultures and colon-cancer-initiating cell (CCIC) lines derived from early-stage CRCs but not from metastatic CRC. CCL25 stimulated cell proliferation by activating AKT signaling. In vivo, systemically injected CCR9+ early-stage CCICs led to the formation of orthotopic gastrointestinal xenograft tumors. Blocking CCR9 signaling inhibited CRC tumor formation in the native gastrointestinal CCL25+ microenvironment, while increasing extraintestinal tumor incidence. NOTCH signaling, which promotes CRC metastasis, increased extraintestinal tumor frequency by stimulating CCR9 proteasomal degradation. Overall, these data indicate that CCL25 and CCR9 regulate CRC progression and invasion and further demonstrate an appropriate in vivo experimental system to study CRC progression in the native colon microenvironment.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

September 2012

Volume

122

Issue

9

Start / End Page

3184 / 3196

Location

United States

Related Subject Headings

  • Transcription Factor HES-1
  • Signal Transduction
  • Receptors, CCR
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Immunology
  • Homeodomain Proteins
 

Citation

APA
Chicago
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MLA
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Chen, H. J., Edwards, R., Tucci, S., Bu, P., Milsom, J., Lee, S., … Lipkin, S. (2012). Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis. J Clin Invest, 122(9), 3184–3196. https://doi.org/10.1172/JCI62110
Chen, Huanhuan Joyce, Robert Edwards, Serena Tucci, Pengcheng Bu, Jeff Milsom, Sang Lee, Winfried Edelmann, Zeynep H. Gümüs, Xiling Shen, and Steven Lipkin. “Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis.J Clin Invest 122, no. 9 (September 2012): 3184–96. https://doi.org/10.1172/JCI62110.
Chen HJ, Edwards R, Tucci S, Bu P, Milsom J, Lee S, et al. Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis. J Clin Invest. 2012 Sep;122(9):3184–96.
Chen, Huanhuan Joyce, et al. “Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis.J Clin Invest, vol. 122, no. 9, Sept. 2012, pp. 3184–96. Pubmed, doi:10.1172/JCI62110.
Chen HJ, Edwards R, Tucci S, Bu P, Milsom J, Lee S, Edelmann W, Gümüs ZH, Shen X, Lipkin S. Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis. J Clin Invest. 2012 Sep;122(9):3184–3196.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

September 2012

Volume

122

Issue

9

Start / End Page

3184 / 3196

Location

United States

Related Subject Headings

  • Transcription Factor HES-1
  • Signal Transduction
  • Receptors, CCR
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice
  • Immunology
  • Homeodomain Proteins