TMPRSS2 is a type II transmembrane-bound serine protease that has gained interest owing to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. PAR (protease-activated receptor)-2 belongs to a family of G-protein-coupled receptors (PAR-1–4) that are activated by specific serine proteases, which are expressed in many normal and malignant cell types. Previous in vitro studies on prostate cancer cells suggest a role for PAR-2 in prostate cancer metastasis. A polyclonal anti-human TMPRSS2 antibody was generated against the TMPRSS2 serine protease domain. The antibody showed specific reactivity with recombinant expressed TMPRSS2, and so was used to extract and purify the cleaved active TMPRSS2 protease from prostate cancer cells. Reverse transcriptase PCR and Western blot analysis were used to show the expression of both TMPRSS2 and PAR-2 in the androgen-dependent LNCaP prostate cancer cell line. Treatment of LNCaP cells with the cellular immunopurified TMPRSS2 protease induced a transient increase in intracellular calcium, which is indicative of G-protein-coupled-receptor activation. This calcium mobilization was inhibited by cellular pre-treatment with a specific PAR-2 antagonist, but not with a PAR-1 antagonist; inhibition of the protease activity also failed to mobilize calcium, suggesting that TMPRSS2 is capable of cleaving and thereby activating the PAR-2 receptor. The calcium mobilization was also inhibited by cellular pre-treatment with suramin or 2-APB (2-aminoethoxydiphenyl borate), indicating that a G-protein pathway is involved and that subsequent calcium release is mainly from intracellular stores. The present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2.
Environmental context. Concern over the presence of antimony (Sb) in the environment because of chemical similarities with arsenic (As) has prompted a need to better understand its environmental behaviour and risks. The present study investigates the bioaccumulation and uptake of antimony in a highly contaminated stream near the Hillgrove antimony–gold mine in NSW, Australia, and reports high Sb (and As) concentrations in many components of the ecosystem consisting of three trophic levels, but limited uptake into aboveground parts of riparian vegetation. The data suggest that Sb can transfer into upper trophic levels of a creek ecosystem, but that direct exposure of creek fauna to creek sediment and soil, water and aquatic autotrophs are more important metalloid uptake routes than exposure via riparian vegetation. Bioaccumulation and uptake of antimony (Sb) were investigated in a highly contaminated stream, Bakers Creek, running adjacent to mining and processing of Sb–As ores at Hillgrove Mine, NSW, Australia. Comparisons with arsenic (As) were included owing to its co-occurrence at high concentrations. Mean metalloid creek rhizome sediment concentrations were 777 ± 115 µg g–1 Sb and 60 ± 6 µg g–1 As, with water concentrations at 381 ± 23 µg L–1 Sb and 46 ± 2 µg L–1 As. Antimony and As were significantly elevated in aquatic autotrophs (96–212 µg g–1 Sb and 32–245 µg g–1 As) but Sb had a lower uptake efficiency. Both metalloids were elevated in all macroinvertebrates sampled (94–316 µg g–1 Sb and 1.8–62 µg g–1 As) except Sb in gastropods. Metalloids were detected in upper trophic levels although biomagnification was not evident. Metalloid transfer to riparian vegetation leaves from roots and rhizome soil was low but rhizome soil to leaf As concentration ratios were up to 2–3 times greater than Sb concentration ratios. Direct exposure to the rhizosphere sediments and soils, water ingestion and consumption of aquatic autotrophs appear to be the major routes of Sb and As uptake for the fauna of Bakers Creek.
Microplastics (MPs) are ubiquitous worldwide, present even in remote areas of the natural environment. Hiking and trail running are a source of MPs on recreational trails in protected environments, which are characterised by high biodiversity and natural, ecological or cultural significance. Our understanding of the risks of microplastic pollution is impeded however by a lack of information on MPs present in the soil environment in such areas. This study characterised the quantity and physicochemical characteristics of MPs in two conservation areas in south-eastern Australia: 1) the adjacent Duval Nature Reserve and Dumaresq Dam Reserve, and 2) the Washpool and Gibraltar Range National Parks. We measured atmospheric deposition over a six-month period in the Reserves, and baseline amounts of MPs on recreational trails in the Reserves and National Parks. Atmospheric deposition averaged 17.4 MPs m-2 day-1 and was dominated by fibres, comprising 84 % of MPs. Microplastics detected on trail surfaces ranged from 162.5 ± 41.6 MPs/linear metre to 168.7 ± 18.5 MPs/linear metre and exhibited a very wide range of physical and chemical characteristics. The majority of MPs on the trail surfaces comprised polyurethane, polyethylene terephthalate and polystyrene, and 47-71 % were fibres. Microplastics were attributed to clothing, footwear, litter, and diffuse sources. Minimising and preventing MP pollution, however, is complex given there are multiple direct and diffuse sources, and several factors influencing increased MP deposition and retention in the environment.
6 February 2014 in Environmental Science and Pollution Research