STC1 expression is associated with tumor growth and metastasis in breast cancer

Abstract

Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several pathologies including retinal degeneration, cerebral ischemia, angiogenesis and inflammation. Aberrant STC1 expression has been reported in breast cancer but the significance of this is not clear. High levels of STC1 expression were found in the aggressive 4T1 murine mammary tumor cells and in the MDA-MB-231 human breast cancer line. To investigate its significance, stable clones with STC1 down-regulation using shRNA were generated in both tumor models. The consequences of STC1 down-regulation on cell proliferation, chemotactic invasion, tumor growth and metastasis were assessed. Down-regulation of STC1 in the 4T1 murine mammary tumor cells had a major impact on mammary tumor growth. This observation was replicated in a second tumor model with the MDA-MB-231 human breast cancer line, with a significant reduction in primary tumor formation and a major inhibition of metastasis as well. Interestingly, in both models, proliferation in vitro was not affected. Subsequent microarray gene expression profiling identified 30 genes to be significantly altered by STC1 down-regulation, the majority of which are associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic analysis of breast cancer datasets revealed that high expression of STC1 is associated with poor survival. This is the first study to show definitively that STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a potential therapeutic target for treatment of breast cancer patients.

Stanniocalcin-1, a new biomarker of glioma progression, is associated with prognosis of patients

“…As a secreted glycoprotein hormone, STC1 was reported to be highly expressed in various types of human malignancies [8][9][10][11]. Enhanced STC1 expression was closely associated with several cancer and poor prognostic outcomes.…”

“…There is also growing evidence that altered STC1 expression patterns may have a role in human cancer [9]. Enhanced STC1 gene or protein expression was closely related to breast cancer [10], colorectal cancer [11], gastric cancer [12], and choroid plexus tumor [13]. Some clinicopathological studies correlate high levels of STC1 in human tumor samples with poor prognostic outcomes.…”

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

“…Although most of studies have focused on the calcium-regulating functions of STC1, increasing evidence suggests that STC1 may also play a major role in carcinoma. High expression of STC1 was frequently detected in human tumor samples of hepatocellular carcinoma (HCC) [16], colorectal cancer [17], lung adenocarcinoma [9], breast cancer [18, 19] and thyroid carcinomas [20], however, low expression of STC1 was found in tumor-derived ovarian epithelial cells [21]. Our previous studies have shown that STC1 is on the decrease in cervical cancer cells for the first time, and that it suppresses cellular multiplication and metastasis of cervical cancer cells likely through NF-κB P65 protein [22].…”

Stanniocalcin-1 Potently Inhibits the Proteolytic Activity of the Metalloproteinase Pregnancy-associated Plasma Protein-A

“…Although some studies report a loss of STC expression, e.g. in breast cancer as a consequence of lost BRCA1 activity (51), the majority of these studies report increased levels of expression (2,52). This is in apparent conflict with a role of the STCs as inhibitors of PAPP-A and hence IGF signaling.…”