Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients

Abstract

African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

Extracellular Vesicles in Prostate Cancer Carcinogenesis, Diagnosis, and Management

“…A correlation was also observed with cancer aggressiveness, metastatic spread, and/or Gleason score ( 181 – 183 ). African-American patients were also demonstrated to have significantly higher amounts of EVs in their plasma and sera than European-American patients and, within their EVs, higher amounts of inhibitors of apoptosis proteins such as survivin, XIAP, and cIAP-2 ( 186 ).…”

Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

“… 166 Tumor-derived EVs can also contribute to the inhibition of the apoptotic cell death by upregulating the expression of anti-apoptotic proteins such as Bcl-xL, 4 survivin, XIAP, and cIAP1,2. 93 , 195 Canine mammary tumor cell–derived EVs had higher levels of miR18a, miR19a, and miR181a compared to canine normal epithelial cell–derived EVs, and it is hypothesized that the miRNAs in cancer-derived EVs might regulate pathways that are important for mammary tumor maintenance and progression, such as cell division, antiapoptotic pathways, and hormone activity mediated by the estrogen receptor. 59 …”

Prostasomas: búsqueda de biomarcadores para la detección temprana del cáncer prostático

“…Por otro lado, la proteína antiapoptótica Survivin pertenece a una familia conocida de oncoproteínas, aislada de vesículas exosómicas derivadas de la sangre, expresada en la mayoría de tumores malignos [27], razón por la cual ha sido estudiada como posible biomarcador en distintos tipos de cáncer, entre ellos CaP. En un estudio realizado en muestras de sangre de pacientes afroamericanos con CaP reportaron un aumento significativo de esta proteína, en comparación de hombres pertenecientes a otros grupos raciales y a los sujetos controles [28]. Es necesario resaltar que el CaP suele ser más agresivo en afroamericanos que en varones de otros grupos étnicos; con este hallazgo se describen diferencias significativas en la biología tumoral de CaP entre grupos étnicos.…”

“…Es necesario resaltar que el CaP suele ser más agresivo en afroamericanos que en varones de otros grupos étnicos; con este hallazgo se describen diferencias significativas en la biología tumoral de CaP entre grupos étnicos. Particularmente, los autores proponen que el aumento de la expresión de Survivina en VEs de pacientes afroamericanos con CaP puede influir en la agresividad del tumor y contribuir con la tasa de mortalidad observada en esta población [28]. Esta proteína podría servir como nuevo biomarcador y posible blanco terapéutico que podría tener utilidad clínica para mejorar la salud de pacientes con CaP, ya que se ha demostrado que la Survivin se encuentra extracelularmente y está contenida en los exosomas [29], además que también se expresa en el CaP y su regulación sensibiliza las células del cáncer a los agentes quimioterapéuticos.…”