Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Exposure to tributyltin chloride induces penis and vas deferens development and increases RXR expression in females of the purple snail (Plicopurpura pansa)

Tributyltin (TBT) and its derivatives are widely used as antifouling paints for ships, resulting in their being released into the marine environment. Aquatic invertebrates, particularly marine gastropods, are extremely sensitive to TBT and undergo changes in the imposition of male secondary sex characteristics in response to exposure. This study aimed to evaluate the development of imposex and the expression of the retinoid X receptor (RXR) in tissues of Plicopurpura pansa (males and females) exposed to tributyltin chloride (TBTCl). The histological results showed a penis-like structure in imposexed female and an undeveloped vas deferens that lacked circular muscular layers. TBTCl treatment increased the messenger RNA (mRNA) of RXR in females with imposex. The highest level of mRNA RXR was found in the digestive gland and penis forming area in females under in vivo exposure compared with control females. These results indicate that TBTCl modulates mRNA levels of RXR in females. mRNA RXR in imposex females and females exposed to TBTCl only was similar to that of males, indicating that RXR might contribute to the development of imposex. To our knowledge, this study is the first to show that TBTCl induces imposex and biphallia in this snail species, and that this effect is accompanied by an increase in RXR expression.El tributilestaño (TBT) y sus derivados se utilizan ampliamente como pinturas antiincrustantes para buques, en el medio marino. Los invertebrados acuáticos, en particular los gasterópodos marinos, extremadamente sensibles a los TBT y sufren cambios en la imposición del sexo secundario masculino características en respuesta a la exposición. El presente estudio tuvo como objetivo evaluar el desarrollo de la expresión del receptor retinoide X (RXR) en tejidos de Plicopurpura pansa (machos y hembras) expuestos al cloruro de tributilestaño (TBTC1). Los resultados histológicos mostraron una estructura tipo pene en impuesta a la mujer y un vaso deferente no desarrollado que carecía de capas musculares circulares. TBTCl tratamiento aumentó el RNA mensajero (ARNm) de RXR en mujeres con imposex. El nivel más alto de ARNm RXR se encontró en la glándula digestiva y en el área de formación de pene en las mujeres bajo in vivo en comparación con las hembras control. Estos resultados indican que TBTCl modula los niveles de mRNA de RXR en mujeres. MRNA RXR en imposex hembras y las mujeres expuestas a TBTCl sólo fue similar a la de los machos, lo que indica que RXR podría contribuir al desarrollo de imposex. A nuestro conocimiento, este estudio es el primero en demostrar que TBTCl induce imposex y biphallia en esta especie de caracol, y que este efecto se acompaña de un aumento de la expresión de RXR

Deregulation of the humoral immune response of the oyster (Crassostrea corteziensis) exposed to naphthalene

Naphthalene is one of the most abundant polycyclic aromatic hydrocarbons (PAH) in aquatic ecosystems, and it can cause alterations in the immune system of organisms that live there. The oyster Crassostrea corteziensis is a species native to the Eastern Tropical Pacific, with economic and ecological importance. In this study, we evaluated the effect of subacute exposure to sublethal concentrations of naphthalene on the parameters of the humoral immune response (lysozyme and phenoloxidase activity, and nitric oxide production) on the oyster C. corteziensis. The results indicated that naphthalene, under the conditions tested, significantly deregulated the parameters evaluated. This could increase susceptibility to infections and therefore affect oyster production.El naftaleno es uno de los hidrocarburos aromáticos policíclicos más abundantes (HAP) en aguas ecosistemas, y puede causar alteraciones en el sistema inmunológico de los organismos que viven allí. Los Crassostrea corteziensis es una especie nativa del Pacífico oriental tropical, con características económicas e importancia ecológica. En este estudio, se evaluó el efecto de la exposición subaguda a sublethal concentraciones de naftaleno en los parámetros de la respuesta inmune humoral (lisozima y actividad fenoloxidasa y producción de óxido nítrico) en la ostra C. corteziensis. Los resultados indicados que el naftaleno, en las condiciones probadas, desreguló significativamente los parámetros evaluados. Esta podría aumentar la susceptibilidad a las infecciones y por lo tanto afectar la producción de ostras

Acetylcholinesterase inhibition and micronucleus frequency in oysters (Crassostrea corteziensis) exposed to chlorpyrifos

Chlorpyrifos (CPF) is an Organophosphorous pesticide (OP) that has been widely used for both agricultural and domestic pest control. To date, there is little information regarding the effects of this pesticide on aquatic organisms, particularly oysters. The aim of this study was to evaluate Acetylcholinesterase (AChE) activity and Micronucleus (MN) frequency in the oyster Crassostrea corteziensis in laboratory exposure with CPF (20, 40, 60, 80, and 160 µg/L) and in a field study. The results showed that AChE was reduced 60 - 82 % in oysters exposed to CPF, relative to the negative control. Similar AChE results were observed in oysters collected from the Boca de Camichín Estuary in Nayarit, Mexico; with respect to genetic damage, evaluated through MN, treatment with CPF did not induce the MN frequency, nor did the oyster from the field study exhibit an increase in this biomarker. These results suggest that C. corteziensis is a sensitive model for evaluating the acute toxicity of OP in laboratory studies as well in the field. In addition, it generates prospects on studying mechanisms through which the oyster could possess resistance to genotoxic agents, as well as its being a reliable model for evaluating the genotoxic effects of xenobiotics through the MN technique.El clorpirifos (CPF) es un pesticida organofosforoso (OP) que ha sido ampliamente utilizado tanto para el control de plagas agrícolas como domésticas. Hasta la fecha, hay poca información sobre los efectos de este pesticida en los organismos acuáticos, particularmente las ostras. El objetivo de este estudio fue evaluar la actividad de la acetilcolinesterasa (AChE) y la frecuencia del micronúcleo (MN) en la ostra Crassostrea corteziensis en exposición de laboratorio con CPF (20, 40, 60, 80 y 160 μg / L) y en un estudio de campo. Los resultados mostraron que la AChE se redujo de 60 a 82% en ostras expuestas a CPF, en relación con el control negativo. Se observaron resultados similares de AChE en las ostras recolectadas en el estuario de Boca de Camichín en Nayarit, México; Con respecto al daño genético, evaluado a través de MN, el tratamiento con CPF no indujo la frecuencia MN, ni la ostra del estudio de campo mostró un aumento en este biomarcador. Estos resultados sugieren que C. corteziensis es un modelo sensible para evaluar la toxicidad aguda de OP en estudios de laboratorio, así como en el campo. Además, genera perspectivas sobre el estudio de mecanismos a través de los cuales la ostra podría poseer resistencia a los agentes genotóxicos, así como su ser un modelo fiable para evaluar los efectos genotóxicos de los xenobióticos a través de la técnica MN