CYP27B1 hydroxylates
25-hydroxyvitamin D3 in position C1α into biologically active
1,25-dihydroxyvitamin D3,
calcitriol.
CYP27B1 is expressed in normal tissues and
tumors. Since
calcitriol indicates anticancer activities and
CYP27B1 expression can be deregulated during malignant progression, we analyzed its expression in
ovarian cancers in relation to pathomorphological features of
tumors and overall survival (OS). Expression of
CYP27B1 was evaluated in 61 ovarian
tumors, 18
metastases and 10 normal ovaries. Normal ovarian epithelium showed the highest levels
CYP27B1 with a significant decrease in its expression in
ovarian cancers. Both poorly differentiated primary
tumors and
metastases showed the lowest level of
CYP27B1 expression, while non-metastasizing
tumors showed a higher
CYP27B1 level than
tumors that developed
metastases. The expression of
CYP27B1 was positively correlated with a lower proliferation rate, lower dynamism of
tumor growth and tumor infiltrating lymphocyte response. Furthermore,
CYP27B1 expression was negatively correlated with
tumor cell modeling of their microenvironment.
CYP27B1 expression was also associated with longer OS time. In summary, our results suggest that local expression of
CYP27B1 in ovarian
tumor cells can modify their behavior and promote a less aggressive phenotype by affecting local concentrations of active of
vitamin D levels within the tumor microenvironment.