IL-17A Promotes and GM-CSF Suppresses Circulating Tumor Cells and Metastasis in Colorectal Cancer

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In a study of the roles of interleukin (IL)-17A and circulating tumor cells in colorectal cancer metastasis, Tseng and colleagues measured mesenteric circulating tumor cells according to colorectal cancer stage in patients and assessed the interaction of circulating tumor cells and IL-17A in a mouse model of metastasis.

Quantification of circulating tumor cells by EpCAM-positive/CD45-negative immunoselection and flow cytometry showed that mesenteric circulating tumor cell levels were higher in stage II disease than in stages I, III, and IV disease, suggesting that circulating tumor cell count after treatment of the primary tumor in early-stage disease may predict risk of metastasis. After invasion of orthotopic tumors in the mouse model, circulating tumor cells exhibited an increase-then-decrease pattern, with a parallel course exhibited by serum IL-17A levels and an opposite course exhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF) levels.

It was found that ablation of IL-17A and administration of recombinant GM-CSF suppressed the increase in circulating tumor cells and prevented metastasis; further, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF resulted in elimination of circulating tumor cells by stimulating host immunity. Measurement of serum IL-17A in colorectal cancer patients showed a correlation with disease-free survival.

The investigators concluded, “Our results showed that [circulating tumor cells] and IL-17A could serve as prognostic markers and therapeutic targets for [colorectal cancer] metastasis.” ■

Tseng J-Y, et al: Clin Cancer Res. March 27, 2014 (early release online).




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