Abstract

Abstract

Activation of the G-protein-coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue-Quest software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER-2 status. Nestin was located together with MT1 in myoepithelial cells in 38 NCa specimens (total n = 42) and in 18 Ca specimens with intact milk ducts. Quantitative evaluation of selected 16 NCa and Ca samples revealed that MT1 levels were higher in invasive Ca sections than in NCa specimens in eight and lower in six cases. Specimens from higher tumor stages (TII/III) with a higher risk of relapse were associated with MT1/nestin co-staining in more than 10% of tumor cells, whereas a lack of co-staining correlated with lower tumor stages. Abundant expression of MT1 and, particularly, coexpression of MT1 with nestin in invading tumor cells in more advanced tumors suggest an important role for this GPCR in the pathogenesis of breast cancer.