A protein critical in heart development may also play a part in colon cancer progression, says a new study.
Investigators from Vanderbilt-Ingram Cancer Center and the Vanderbilt Eye Institute suggests that the protein BVES (blood vessel endocardial substance), which also is key in regulating corneal cells, may be a therapeutic target for halting colon cancer metastasis.
The study further suggests that BVES may be important more broadly in many, or most, epithelial cancers.
Ophthalmologist Min Chang, M.D., studied the healing process in the cornea, which is perhaps the most highly regulated epithelium in the body.
From collaborative studies with David Bader, Ph.D., who discovered BVES and showed its importance in heart development, Chang found that BVES was highly expressed and regulated in corneal cells.
When BVES is disrupted in corneal cells, they become disorganized, almost "cancer-like," noted Chang, an assistant professor of Ophthalmology and Visual Sciences and co-author on the study.
Chang then brought these findings to the attention of colleague Christopher Williams, M.D., Ph.D., assistant professor of Medicine and Cancer Biology and co-author on the study.
"When he described these cells, it sounded a lot like the way cancer cells looked when they were undergoing metastasis. So it seemed reasonable to look in cancer for BVES-dependent phenotypes," Williams said.
Chang and Williams teamed up with the lab of Daniel Beauchamp, M.D., to assess BVES expression in human colorectal cancers. They found that BVES levels were very low in all stages of colon cancer.
They also noted decreased BVES levels in many other types of epithelial cancers (including breast) and in several colorectal cancer cell lines.
In cell experiments, the researchers showed that treating cells with a "demethylating" agent (the drug decitabine, which is currently used to treat myelodysplastic disorders) restored BVES expression.
When BVES was expressed in colorectal cancer cell lines, they became more epithelial in nature and their tumour-like characteristics (in cell experiments and in animal models) decreased.
These findings suggest that treatment with agents to increase BVES levels might provide a way to decrease aggressive behaviours of colorectal and other epithelial cancers.
The findings appear in the October issue of the Journal of Clinical Investigation.