Colorectal cancer is a major health concern.
Vitamin D deficiency is associated with high colorectal cancer incidence and mortality, suggesting a protective effect of vitamin D against this disease.
Given the strong influence of tumor stroma on cancer progression, Dr Gemma Ferrer-Mayorga and colleagues investigated the potential effects of the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on colorectal cancer stroma.
Expression of vitamin D receptor and 2 of the 1,25(OH)2D3 target genes was analyzed in 658 patients with colorectal cancer with prolonged clinical follow-up.
The researchers noted that 1,25(OH)2D3 effects on primary cultures of patient-derived colon normal fibroblasts, and cancer-associated fibroblasts were studied using collagen gel contraction and migration assays and global gene expression analyses.
|Expression of 2 genes correlated with stromal vitamin D receptor expression |
Publicly available data sets were used to correlate the 1,25(OH)2D3-associated gene signature in cancer-associated fibroblasts with colorectal cancer outcome.
The researchers noted that high VDR expression in tumor stromal fibroblasts was associated with better overall survival, and progression-free survival in colorectal cancer, independently of its expression in carcinoma cells.
The team observed that 1,25(OH)2D3 inhibited the protumoral activation of normal fibroblasts and cancer-associated fibroblasts, and imposed in cancer-associated fibroblasts a 1,25(OH)2D3-associated gene signature that correlated with longer overall survival and disease-free survival in colorectal cancer.
Furthermore, expression of 2 genes from the signature, CD82 and S100A4, correlated with stromal vitamin D receptor expression and clinical outcome in our cohort of patients with colorectal cancer.
Dr Ferrer-Mayorga, "1,25(OH)2D3 has protective effects against colorectal cancer through the regulation of stromal fibroblasts."
"Accordingly, expression of vitamin D receptor and 1,25(OH)2D3-associated gene signature in stromal fibroblasts predicts a favorable clinical outcome in colorectal cancer."
"Therefore, treatment of patients with colorectal cancer with vitamin D receptor agonists could be explored even in the absence of VDR expression in carcinoma cells."