Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance

Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.

Effect of pretreatment on the formation of 5-chloromethyl furfural derived from sugarcane bagasse

Chloromethylfurfural (CMF), a valuable intermediate for the production of chemicals and fuel, can be derived in high yields from the cellulose component of biomass. This study examined the effect of sugar cane bagasse components and biomass architecture on CMF/bio-oil yield using a HCl/dichloroethane biphasic system. The type of pretreatment affected bio-oil yield, as the CMF yield increased with increasing glucan content. CMF yield reached 81.9% with bagasse pretreated by acidified aqueous ionic liquid, which had a glucan content of 81.6%. The lignin content of the biomass was found to significantly reduce CMF yield, which was only 62.3% with acid-catalysed steam exploded sample having a lignin content of 29.6%. The change of CMF yield may be associated with fibre surface changes as a result of pretreatment. The hemicellulose content also impacted negatively on CMF yield. Storage of the bio-oil in chlorinated solvents prevented CMF degradation.