Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma

Abstract

Stanniocalcin 2 (STC2) is a secreted glycoprotein of as yet unknown functions. We investigated STC2 in human neuroblastoma, the most common solid extra-cranial tumor of infancy. In primary tumor samples, we found that expression of STC2 is associated with the metastatic Stages 4 and 4s and MYCN expression. In vitro, however, we demonstrate that cell proliferation is reduced by STC2 due to an increase in the basal apoptosis rate of the transfected cells. On the other hand, in vitro assays showed that STC2-transfected neuroblastoma cells have an increased invasive potential and display higher activity of collagen-degrading matrix metalloproteinase 2 (MMP2). Using experimental tumors on the chick chorioallantoic membrane (CAM), we observed that STC2 expressing cells show signs of emigration from the solid tumor and destroy blood vessels of the CAM, giving rise to massively bleeding tumors. Erosion of blood vessels was also seen when purified STC2 protein was applied on the CAM. Taken together, we demonstrate a dual role for STC2 in neuroblastoma. It reduces proliferation of tumor cells in vitro, but increases the invasive potential and induces bleeding, and thereby may facilitate early metastasis. The potential of STC2 as a surrogate marker for metastatic neuroblastoma calls for further investigation. ' 2009 UICC

Stanniocalcin 2 Is a Negative Modulator of Store-Operated Calcium Entry

“…Although there is a clear correlation between STC2 levels and cancer progression, most of these studies have not addressed the functional significance of elevated STC2 expression. Some reports using cancer cell lines, however, have proposed that STC2 promotes the invasiveness and metastasis of cancer cells, although the exact mechanism for this effect is not clear (26,29,53). Our current study has identified SOCE as an important molecular pathway regulated by STC2, with STIM1 as a direct binding partner.…”

“…While STC2 does not appear to play a physiologic role in the endocrine regulation of Ca 2ϩ homeostasis, numerous studies have demonstrated a link between STC2 expression and a variety of different cancers, including breast, prostate, renal, colorectal, and ovarian carcinomas (4,5,22,36,51). Other recent work has suggested that STC2 promotes invasiveness and metastasis in cancer cells (26,29,53). However, despite a clear role in human disease, the molecular function and targets of mammalian STC2 remain largely unknown.…”

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

“…It has been reported that STC2 expression was upregulated in various tumors, including breast cancer [16,17], prostate cancer [18], esophageal squamous cell carcinoma (ESC) [19], gastric cancer [20], colorectal cancer [21], renal cell carcinoma (RCC) [22] and neuroblastoma [23]. Clinical and pathological studies reveal that STC2 overexpression correlates to advanced tumor grade, tumor invasiveness, metastasis and poor prognosis in prostate cancer, ESC, gastric cancer, colorectal cancer and RCC [18].…”

Matrix metalloproteinase 2 promotes cell growth and invasion in colorectal cancer

“…Matrix metalloproteinase-2 (MMP2) is a member of the matrix metalloproteinase (MMP) family, which is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, angiogenesis [2,3], and tissue remodeling, as well as in disease processes, such as arthritis and tumor invasion and metastasis [4]. In the past few years, MMPs overexpression has been intensively investigated as potential biomarkers and unfavorable factors in a range of types of cancer including CRC [5][6][7][8][9][10].…”