FGF-10 plays an essential role in the growth of the fetal prostate

AbstractInduction and branching morphogenesis of the prostate are dependent on androgens, which act via the mesenchyme to induce prostatic epithelial development. One mechanism by which the mesenchyme may regulate the epithelium is through secreted growth factors such as FGF-10. We have examined the male reproductive tract of FGF-10−/− mice, and at birth, most of the male secondary sex organs were absent or atrophic, including the prostate, seminal vesicle, bulbourethral gland, and caudal ductus deferens. Rudimentary prostatic buds were occasionally observed in the prostatic anlagen, the urogenital sinus (UGS) of FGF-10−/− mice. FGF-10−/− testes produced sufficient androgens to induce prostatic development in control UGS organ cultures. Prostatic rudiments from FGF-10−/− mice transplanted into intact male hosts grew very little, but showed some signs of prostatic differentiation. In cultures of UGS, the FGF-10 null phenotype was partially reversed by the addition of FGF-10 and testosterone, resulting in the formation of prostatic buds. FGF-10 alone did not stimulate prostatic bud formation in control or FGF-10−/− UGS. Thus, FGF-10 appears to act as a growth factor which is required for development of the prostate and several other accessory sex organs

An ALMA survey of Sub-millimeter Galaxies in the Extended Chandra Deep Field South: Physical properties derived from ultraviolet-to-radio modelling

[abridged] The ALESS survey has followed-up a sample of 122 sub-millimeter sources in the Extended Chandra Deep Field South at 870um with ALMA, allowing to pinpoint the positions of sub-millimeter galaxies (SMGs) to 0.3'' and to find their precise counterparts at different wavelengths. This enabled the first compilation of the multi-wavelength spectral energy distributions (SEDs) of a statistically reliable survey of SMGs. In this paper, we present a new calibration of the MAGPHYS modelling code that is optimized to fit these UV-to-radio SEDs of z>1 star-forming galaxies using an energy balance technique to connect the emission from stellar populations, dust attenuation and dust emission in a physically consistent way. We derive statistically and physically robust estimates of the photometric redshifts and physical parameters for the ALESS SMGs. We find that they have a median stellar mass $M_\ast=(8.9\pm0.1)\times10^{10} M_\odot$, SFR$=280\pm70 M_\odot$/yr, overall V-band dust attenuation $A_V=1.9\pm0.2$ mag, dust mass M_\rm{dust}=(5.6\pm1.0)\times10^8 M_\odot, and average dust temperature Tdust~40 K. The average intrinsic SED of the ALESS SMGs resembles that of local ULIRGs in the IR range, but the stellar emission of our average SMG is brighter and bluer, indicating lower dust attenuation, possibly because they are more extended. We explore how the average SEDs vary with different parameters, and we provide a new set of SMG templates. To put the ALESS SMGs into context, we compare their stellar masses and SFRs with those of less actively star-forming galaxies at the same redshifts. At z~2, about half of the SMGs lie above the star-forming main sequence, while half are at the high-mass end of the sequence. At higher redshifts (z~3.5), the SMGs tend to have higher SFR and Mstar, but the fraction of SMGs that lie significantly above the main sequence decreases to less than a third.Comment: 22 pages, 14 figures, 2 tables. Accepted for publication in the Astrophysical Journal. The new MAGPHYS model libraries used in this paper will appear in www.iap.fr/magphys. The SMG SED templates shown in Section 6.1 are available at http://astronomy.swinburne.edu.au/~ecunha/ecunha/SED_Templates.htm

Reduction of pro-tumorigenic activity of human prostate cancer-associated fibroblasts using Dlk1 or SCUBE1

SUMMARY Human prostatic cancer-associated fibroblasts (CAFs) can elicit malignant changes in initiated but non-tumorigenic human prostate epithelium, demonstrating that they possess pro-tumorigenic properties. We set out to reduce the pro-tumorigenic activity of patient CAFs using the Dlk1 and SCUBE1 molecules that we had previously identified in prostate development. Our hypothesis was that mesenchymally expressed molecules might reduce CAF pro-tumorigenic activity, either directly or indirectly. We isolated primary prostatic CAFs and characterised their expression of CAF markers, expression of Notch2, Dlk1 and SCUBE1 transcripts, and confirmed their ability to stimulate BPH1 epithelial cell proliferation. Next, we expressed Dlk1 or SCUBE1 in CAFs and determined their effects upon tumorigenesis in vivo following recombination with BPH1 epithelia and xenografting in SCID mice. Tumour size was reduced by about 75% and BPH1 proliferation was reduced by about 50% after expression of Dlk1 or SCUBE1 in CAFs, and there was also a reduction in invasion of BPH1 epithelia into the host kidney. Inhibition of Notch signalling, using inhibitor XIX, led to a reduction in BPH1 cell proliferation in CAF-BPH1 co-cultures, whereas inhibition of Dlk1 in NIH3T3-conditioned media led to an increase in BPH1 growth. Our results suggest that pro-tumorigenic CAF activity can be reduced by the expression of developmental pathways

Enzymically attaching oligosaccharide-linked ‘cargoes’ to cellulose and other commercial polysaccharides via stable covalent bonds

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An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South : The Redshift Distribution and Evolution of Submillimeter Galaxies

Accepted by ApJ. 45 pages, 16 figuresWe present the first photometric redshift distribution for a large unbiased sample of 870um selected submillimeter galaxies (SMGs) with robust identifications based on observations with the Atacama Large Millimeter Array (ALMA). In our analysis we consider 96 SMGs in the Extended Chandra Deep Field South, 77 of which have 4-19 band, optical-near-infrared, photometry. We model the Spectral Energy Distributions (SEDs) for these 77 SMGs, deriving a median photometric redshift of z=2.3+/-0.1. The remaining 19 SMGs have insufficient optical or near-infrared photometry to derive photometric redshifts, but a stacking analysis of IRAC and Herschel observations confirms they are not spurious. Assuming these sources have an absolute H-band magnitude distribution comparable to that of a complete sample of z~1-2 SMGs, we demonstrate that the undetected SMGs lie at higher redshifts, raising the median redshift for SMGs to z=2.5+/-0.2. More critically we show that the proportion of galaxies undergoing an SMG phase at z>3 is 35+/-5% of the total population. We derive a median stellar mass for SMGs of Mstar=(8+/-1)x10^10Mo, but caution that there are significant systematic uncertainties in our stellar mass estimate, up to x5 for individual sources. We compare our sample of SMGs to a volume-limited, morphologically classified sample of ellipticals in the local Universe. Assuming the star formation activity in SMGs has a timescale of ~100Myr we show that their descendants at z~0 would have a space density and M_H distribution which are in good agreement with those of local ellipticals. In addition the inferred mass-weighted ages of the local ellipticals broadly agree with the look-back times of the SMG events. Taken together, these results are consistent with a simple model that identifies SMGs as events that form most of the stars seen in the majority of luminous elliptical galaxies at the present day.Peer reviewe

Stromal expression of decorin, Semaphorin6D, SPARC, Sprouty1 and Tsukushi in developing prostate and decreased levels of decorin in prostate cancer.

BACKGROUND AND AIM: During prostate development, mesenchymal-epithelial interactions regulate organ growth and differentiation. In adult prostate, stromal-epithelial interactions are important for tissue homeostasis and also play a significant role in prostate cancer. In this study we have identified molecules that show a mesenchymal expression pattern in the developing prostate, and one of these showed reduced expression in prostate cancer stroma. METHODOLOGY AND PRINCIPAL FINDINGS: Five candidate molecules identified by transcript profiling of developmental prostate mesenchyme were selected using a wholemount in situ hybridisation screen and studied Decorin (Dcn), Semaphorin6D (Sema6D), SPARC/Osteonectin (SPARC), Sprouty1 (Spry-1) and Tsukushi (Tsku). Expression in rat tissues was evaluated using wholemount in situ hybridisation (postnatal day (P) 0.5) and immunohistochemistry (embryonic day (E) E17.5, E19.5; P0.5; P6; 28 & adult). Four candidates (Decorin, SPARC, Spry-1, Tsukushi) were immunolocalised in human foetal prostate (weeks 14, 16, 19) and expression of Decorin was evaluated on a human prostate cancer tissue microarray. In embryonic and perinatal rats Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi were expressed with varying distribution patterns throughout the mesenchyme at E17.5, E19.5, P0.5 and P6.5. In P28 and adult prostates there was either a decrease in the expression (Semaphorin6D) or a switch to epithelial expression of SPARC, and Spry-1, whereas Decorin and Tsukushi were specific to mesenchyme/stroma at all ages. Expression of Decorin, SPARC, Spry-1 and Tsukushi in human foetal prostates paralleled that in rat. Decorin showed mesenchymal and stromal-specific expression at all ages and was further examined in prostate cancer, where stromal expression was significantly reduced compared with non-malignant prostate. CONCLUSION AND SIGNIFICANCE: We describe the spatio-temporal expression of Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate and observed similar mesenchymal expression patterns in rat and human. Additionally, Decorin showed reduced expression in prostate cancer stroma compared to non-malignant prostate stroma