Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment: Decreased tumor metastasis in a breast cancer model

Stephania Libreros, Ramon Garcia-Areas, Yoshimi Shibata, Roberto Carrio, Marta Torroella-Kouri, Vijaya Iragavarapu-Charyulu

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Disseminated metastasis accounts for over 90% of breast cancer deaths. Recently, elevated serum levels of a glycoprotein known as chitinase-3 like-protein-1 (CHI3L1) has been correlated with poor prognosis and shorter survival of patients with metastatic breast cancer. In this study, we show that there are increased levels of CHI3L1 in plasma of tumor-bearing mice and that both tumor cells and immune cells express and secrete CHI3L1. However, the biological and physiological functions of CHI3L1 are still unclear. We demonstrate that while CHI3L1 has an inhibitory role in the expression of interferon-gamma (IFN-γ), CHI3L1 up-regulates pro-inflammatory mediators, C-chemokine ligand 2 (CCL2), chemokine CX motif ligand 2 (CXCL2) and matrix metalloproteinase-9 (MMP-9) all of which contribute to tumor growth and metastasis. We found that in vitro inhibition of CHI3L1 by siRNA suppressed the production of CCL2, CXCL2 and MMP-9 by macrophages. In vivo treatment of mammary tumor-bearing mice with chitin (β-(1-4)-poly-N-acetyl D-glucosamine), a TH 1 adjuvant and a ligand for CHI3L1, promoted immune effector functions with increased production of IFN-γ and decreased CCL2, CXCL2 and MMP-9 expression. In vivo administration of chitin to mammary tumor-bearing mice significantly decreased lung metastasis. These studies show that CHI3L1 plays a role in tumor progression and that chitin can inhibit the pleiotropic effects of CHI3L1 giving support to the idea that CHI3L1 is a useful therapeutic target for treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)377-386
Number of pages10
JournalInternational Journal of Cancer
Volume131
Issue number2
DOIs
StatePublished - Jul 15 2012

Keywords

  • CCL2
  • chitin
  • chitinase-3-like-1 protein
  • CXCL2
  • immunosuppression
  • metastasis
  • MMP-9

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Libreros, S., Garcia-Areas, R., Shibata, Y., Carrio, R., Torroella-Kouri, M., & Iragavarapu-Charyulu, V. (2012). Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment: Decreased tumor metastasis in a breast cancer model. International Journal of Cancer, 131(2), 377-386. https://doi.org/10.1002/ijc.26379