Interleukin 11 as a marker of colorectal cancer-associated fibroblasts

Interleukin 11 as a marker of colorectal cancer-associated fibroblasts

IL-11 is known to promote the development of colorectal cancer in humans and mice, but when and where IL-11 is expressed during cancer development is unknown. "To address these questions experimentally, we generated reporter mice that express the green fluorescent protein (EGFP) gene in interleukin 11 (IL-11)-producing (IL11+) cells in vivo. We found IL-11+ cells in the colons of this murine colitis-associated colorectal cancer model," said the lead author of a study published in Nature Communications. "The IL-11+ cells were absent from the colon under normal conditions but rapidly appeared in the tissues of mice with colitis and colorectal cancer."

In the study, the authors characterized the IL-11+ cells by flow cytometry and found that most IL-11+ cells express stromal cell surface markers, such as Thy1, podoplanin, and Sca-1, suggesting that IL-11+ cells are stromal fibroblasts.

RNA-seq analysis revealed that the expression of approximately 350 genes was elevated in IL-11+ fibroblasts compared IL-11- fibroblasts. These genes were also elevated in murine and human colorectal cancer tissues in vivo. IL-11 released from IL-11+ cells induced activation signals in nearby tumor cells and fibroblasts in a paracrine or autocrine manner. Thus, IL-11+ fibroblasts and tumor cells constitute the tumor microenvironment that supports tumor growth.

"We looked at human cancer databases and found that elevated expression of genes enriched in IL-11+ fibroblasts correlate with short duration of disease-free survival. We think IL-11+ fibroblasts can be new therapeutic targets for treating human colorectal cancer," said the senior author of the study.