PMID:22363577

Citation	Bais, MV, Nugent, MA, Stephens, DN, Sume, SS, Kirsch, KH, Sonenshein, GE and Trackman, PC (2012) Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts. PLoS ONE 7:e31188
Abstract	Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations.
Links	PubMed PMC3280126 Online version:10.1371/journal.pone.0031188
Keywords	Alginates; Animals; Apoptosis/drug effects; Breast Neoplasms/enzymology; Breast Neoplasms/pathology; Caspase 3/metabolism; Cell Line, Tumor; Cell Proliferation/drug effects; Delayed-Action Preparations; Extracellular Signal-Regulated MAP Kinases/metabolism; Female; HEK293 Cells; Histones/metabolism; Humans; In Situ Nick-End Labeling; Ki-67 Antigen/metabolism; Kinetics; Mice; Microspheres; Peptides/pharmacology; Phosphorylation/drug effects; Protein-Lysine 6-Oxidase/pharmacology; Recombinant Proteins/pharmacology; Tumor Markers, Biological/metabolism; Xenograft Model Antitumor Assays
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:LOXL1		GO:0006915: apoptotic process	ECO:0000314:		P		Figure 9 shows LOX-PP inhibits Ras effector Erk1/2 phosphorylation in vivo.	complete CACAO 6281

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