Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

Abstract Background ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells.

Two New Species of Stenophragma Skuse from Western Australia (Diptera, Mycetophilidae, Sciophilinae)

Stenophragma Skuse was originally described for S. meridianum (Skuse), from Australia. Since then seventeen species have been added to the genus-from Brazil, Ecuador, Peru, Bolivia, Paraguay, Chile, Argentina, and Canada. We add two new species to the genus Stenophragma-S. bickeli n.sp. and S. collessi n.sp.-from Western Australia. An identification key for the Australian species of Stenophragma is provided. Comments are made about possible relationships among these new species and the remaining Australasian species of the genus. OLIVEIRA, SARAH SIQUEIRA, AND DALTON DE SOUZA AMORIM. 2012. Two new species of Stenophragma Skuse from Western Australia (Diptera, Mycetophilidae, Sciophilinae). Records of the Australian Museum 64(2): 149-158.