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BackgroundTumor cell tissue factor (TF)-initiated coagulation supports hematogenous metastasis by fibrin formation, platelet activation and monocyte/macrophage recruitment. Recent studies identified host anticoagulant mechanisms as a major impediment to successful hematogenous tumor cell metastasis.ObjectiveHere we address mechanisms that contribute to enhanced metastasis in hyperthrombotic mice with functional thrombomodulin deficiency (TM(Pro) mice).MethodsPharmacological and genetic approaches were combined to characterize relevant thrombin targets in a mouse model of experimental hematogenous metastasis.ResultsTF-dependent, but contact pathway-independent, syngeneic breast cancer metastasis was associated with marked platelet hyperreactivity and formation of leukocyte-platelet aggregates in immune-competent TM(Pro) mice. Blockade of CD11b or genetic deletion of platelet glycoprotein Ibα excluded contributions of these receptors to enhanced platelet-dependent metastasis in hyperthrombotic mice. Mice with very low levels of the endothelial protein C receptor (EPCR) did not phenocopy the enhanced metastasis seen in TM(Pro) mice. Genetic deletion of the thrombin receptor PAR1 or endothelial thrombin signaling targets alone did not diminish enhanced metastasis in TM(Pro) mice. Combined deficiency of PAR1 on tumor cells and the host reduced metastasis in TM(Pro) mice.ConclusionsMetastasis in the hyperthrombotic TM(Pro) mouse model is mediated by platelet hyperreactivity and contributions of PAR1 signaling on tumor and host cells.

The possible role of dietary flax on prepubertal development of mammary glands and bone resorption was investigated in gilts. Fifty-seven gilts were fed 1 of 4 diets from 88 d of age until slaughter (d 212 [+ or -] 1). Diets were control without flax (n = 14); 10% flaxseed supplementation (n = 13); 6.5% flaxseed meal supplementation (n = 15); and 3.5% flaxseed oil supplementation (n = 15). All diets were isonitrogenous and isocaloric. Jugular blood samples were obtained on d 78 and 210 to establish the fatty acid profile and to determine the concentrations of prolactin, estradiol, and cross-linked N-telopeptides of type I collagen. At slaughter, the mammary glands were excised, parenchymal and extraparenchymal tissues were dissected, and the composition of the parenchymal tissue (protein, fat, DM, and DNA) was determined. Histochemical analyses of the mammary parenchyma were performed, and fatty acid profiles in the extraparenchymal tissue were evaluated. Dietary flax increased (P [less than or equal to] 0.001) the concentrations of PUFA and decreased those of SFA (P < 0.01) and MUFA (P [less than or equal to] 0.001) in plasma and extraparenchymal tissues, which was largely due to the inclusion of 10% flaxseed or 3.5% flaxseed oil (P [less than or equal to] 0.01) but not 6.5% flaxseed meal. Circulating concentrations of prolactin and estradiol were unaltered by treatments (P > 0.1), but concentrations of cross-linked N-telopeptides of type I collagen tended to be greater (P < 0.1) in flax-supplemented gilts. The DM content of parenchymal tissue was the only mammary compositional value affected, showing an increase with flax addition (P < 0.05). No change (P [greater than or equal to] 0.1) in the bromodeoxyuridine labeling index or estrogen receptor localization was observed with treatments. Dietary supplementation with flax as seed, meal, or oil, therefore, brought about the expected changes in the fatty acid profile but had no beneficial effects on mammary development or bone resorption. Key words: bone resorption, flaxseed, mammary development, mammary gland, pig, prepubertal female

An experiment was conducted to determine growth performance, carcass characteristics, and fat quality of growing-finishing pigs fed diets based on short-season corn hybrids. Twenty-four individually housed, Cotswold, growing pigs with an initial BW of 41.4 (SD = 1.4) kg were blocked by BW and sex and randomly allotted from within block to 1 of 3 diets to give 8 replicate pigs per diet. Experimental diets consisted of a control based on barley and 2 diets based on corn as the main energy sources. A 3-phase feeding program for 20 to 50 kg (phase I), 50 to 80 kg (phase II), and 80 to 110 kg (phase III) of BW was used. Diets for each phase contained approximately 3.5 Mcal/kg of DE, with total lysine of 0.95, 0.75, and 0.64% in phase I, II, and III diets, respectively. Average daily gain, ADFI, and G:F were monitored weekly during each phase. Pigs were slaughtered after reaching a minimum BW of 100 kg to determine carcass characteristics. There were no effects of diet on ADG, ADFI, and G:F (0.45 [+ or -] 0.02, 0.34 [+ or -] 0.02, and 0.31 [+ or -] 0.02 for phase I, II, and III, respectively). Carcass length, dressing percent, LM area, loin depth, backfat thickness, belly firmness, and L *, b *, and a * fat color were not different across dietary treatments. Pigs fed one corn variety had no differences in fatty acid profile with barley-fed pigs, whereas those fed the other variety of corn had a greater (P < 0.05) concentration of PUFA in their backfat. The results indicate that growth performance, carcass characteristics, and fat quality of pigs fed diets based on short-season corn hybrids and those fed the barley-based diet were not different. Key words: carcass quality, corn, growth performance, pig