Anti-ACP5 (aa 221-325) polyclonal antibody

Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this "deterministic" hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.

Chronic inflammatory diseases affect bone and teeth health tremendously. Characterized by osteolytic lesion and hyperactive osteoclastogenesis, inflammatory bone diseases are short of effective therapeutics and therefore highlight the importance of understanding pathogenesis and developing ideal medications. Reactive oxygen species (ROS) play a prominent role in the innate immune response of activated macrophages, as well as in the physiological signaling of osteoclasts (OCs) differentiation. N-acetylcysteine (NAC) is a potent ROS scavenger and a potential option for treating diseases characterized by excessive ROS generation. However, whether NAC can protect physiological bone remodeling from in vivo inflammatory conditions is largely undefined. We applied NAC treatment on lipopolysaccharide (LPS)-induced inflammatory osteolysis mice model and found that NAC could attenuate bone erosion and protect mice against LPS-induced osteolysis, due to the suppressive effect on osteoclastogenesis and stimulated effect on osteogenesis. Moreover, in vitro study demonstrated that, in OC precursors (pre-OCs), LPS-stimulated expressions of OC marker genes, such as tartrate-resistant acid phosphatase type 5 (Acp5), cathepsin K (Ctsk), OC stimulatory transmembrane protein (Oc-stamp), dendritic cell-specific transmembrane protein (Dc-stamp), and nuclear factor of activated T cells 1 (NFATc1), were all reduced because of the NAC pretreatment, thereby adversely affecting OC function including F-actin ring formation and bone resorption. Further mechanism study showed that NAC blocked LPS-induced ROS formation in both macrophages and pre-OCs, cutting off the LPS-stimulated autocrine/paracrine mechanism during inflammatory osteolysis. Our findings reveal that NAC attenuates inflammatory osteolysis via the elimination of ROS formation during LPS-stimulated osteoclastogenesis, and provide a potential therapeutic approach to treat inflammatory bone disease.