Non-cancer cells define aggressive colorectal cancer

Non-tumor cells can interact with nearby cancer cells to cause an aggressive subtype of colorectal cancer, reports two papers published online this week in Nature Genetics. The papers featured studies of human cancer cells transplanted into mice and may help physicians to determine the correct treatments for different colorectal cancer patients.

The outcome from colorectal cancer (CRC) differs dramatically between patients. Nearly half of patients with advanced CRC are resistant to therapy and relapse during treatment. In two independent studies, researchers used profiles of gene expression from tumors and adjacent stromal (normal) cells to identify a specific gene expression signature that predicts poor prognosis in patients.

Claudio Isella and colleagues analyzed data from CRC patients and found that many of the genes that are highly expressed in patients with poor outcome may be expressed by the stromal cells. They tested this prediction using available data from mice that had been transplanted with human cancer cells, and found that the highly expressed genes came from the surrounding mouse tissue rather than the cancerous human tissue.

In a separate study, Eduard Batlle and colleagues identified a similar gene expression signature, derived from the surrounding stromal cells, which correlated with poor patient outcome. They found that the cross-talk between tumor and normal cells was mediated by the transforming growth factor beta (TGF-β) signaling pathway. The authors then established patient-derived tumor “organoids”; miniature colons in a dish that can mimic what happens inside the patient. After transplantation of organoid cells into mice, the authors showed that tumor progression could be slowed by treatment with a TGF-β pathway blocker currently in clinical trials.