Interleukin-17A modulates circulating tumor cells in tumor draining vein of colorectal cancers and affects metastases

Ju Yu Tseng, Chih Yung Yang, Shu Ching Liang, Ren Shyan Liu, Shung Haur Yang, Jen Kou Lin, Yuh Min Chen, Yu Chung Wu, Jeng Kai Jiang*, Chi Hung Lin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Purpose: Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC. Experimental Design: CTCs were quantified using EpCAM-positive/CD45-negative immunoselection and flow cytometry in patients with CRC. A mouse model was used to investigate the mechanistic roles of CTCs and interleukin (IL)-17A in metastasis. Results: The number of mesenteric CTCs obtained from stage II patients was higher than that obtained from patients in stages I, III, and IV. In addition, following invasion of orthotopically implanted tumors in our mouse model, we found that CTCs exhibited an increase-then-decrease pattern, accompanied by corresponding changes in serum IL-17A levels and opposing changes in serum granulocyte macrophage colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host immunity. Notably, serum levels of IL-17A were also correlated with disease-free survival in patients with CRC. Conclusions: Our results showed that CTCs and IL-17A could serve as prognostic markers and therapeutic targets for CRC metastasis.

Original languageEnglish
Pages (from-to)2885-2897
Number of pages13
JournalClinical Cancer Research
Volume20
Issue number11
DOIs
StatePublished - 1 Jun 2014

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