Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model

INTRODUCTION: Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage (M2-Mϕ) population and are associated with poor prognosis in various cancers. In the present study, we attempted to assess whether M2-Mϕs derived from bone marrow stimulate the promotion and progression of mammary tumors. METHODS: 4T1 murine mammary carcinoma cells were injected either alone or coupled with M2-Mϕs into the mammary fat pads of syngeneic female Balb/C mice. M2-Mϕs were prepared by treating monocytes isolated from female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using an in vivo imaging system and the expression of cell proliferation-related, angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was immunohistochemically analyzed. To evaluate the effects of the crosstalk between 4T1 cells and M2-Mϕs on the secretion and mRNA expression of cytokines and the migration of monocytes, 4T1 cells and M2-Mϕs were co-cultured and cytokine antibody array, real-time RT-PCR, and trans-well migration assays were conducted. RESULTS: The co-injection of M2-Mϕs into the mammary fat pads of mice increased solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration of CD45(+ )leukocytes into tumor tissues. The proportions of Ki-67(+ )proliferating cells and the expression of hypoxia inducible factor-1α, vascular endothelial cell growth factor A, CD31, vascular endothelial cell growth factor C, and lymphatic vessel endothelial receptor-1 were increased significantly in the tumor tissues of mice co-injected with 4T1 cells and M2-Mϕs. The in vitro results revealed that the proliferation of 4T1 cells, the migration of monocytes, and the secretion of granulocyte colony-stimulating factor, IFNγ, IL-1α, IL-2, IL-16, IFNγ-induced protein-10, keratinocyte-derived chemokine, macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were increased when 4T1 cells were co-cultured with M2-Mϕs, as compared with when the 4T1 cells were cultured alone. CONCLUSION: The crosstalk between 4T1 cells and M2-Mϕs increased the production of cytokines, which may have induced immune cell infiltration into tumor tissues, tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby increasing solid tumor growth and lung metastasis

Effects of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility in growing pigs compared to those of defatted mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble

Objective: To investigate effect of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility compared to those of dried mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble in growing pigs. Methods: A total of 12 crossbred ([LandracexYorkshire]xDuroc) growing pigs with average body weight of 28.70 +/- 0.32 kg were surgically equipped with simple T-cannulas. A total of 12 pigs were assigned to individual metabolic crates and allotted to one of four treatments with 3 replicates in a fully randomized design. Results: Apparent ileal digestibility (AID) of dry matter (DM) was the highest in pigs fed HML diet. AIDs of crude protein (CP) were higher in pigs fed HML and DMLM diets than those in pigs fed the other two diets. AID of total amino acid was higher (p = 0.06) in pigs fed HML diet. AIDs of lysine (Lys), methionine (Met), and threonine (Thr) were similar in pigs fed DMLM and HML diets, but were higher (p = 0.05, p<0.05, and p = 0.05, respectively) than those in pigs fed FPBM or HFS diet. Pigs fed HML diet had higher standardized ileal digestibilities (SIDs) of DM and CP (p<0.05 and p<0.05, respectively) compared to pigs fed the other FPBM and HFS diets. SIDs of total amino acid were not different (p = 0.06) between treatments. For SIDs of Lys, Met, and Thr, pigs fed HML and DMLM diets showed higher SIDs (p = 0.05, p<0.05, and p<0.05, respectively) than pigs fed FPBM and HFS diets. SIDs of non-essential amino acids (aspartic acid, glycine, and alanine) were higher (p<0.05, p< 0.05, and p<0.05, respectively) in pigs fed HML, FPBM, and DMLM diets than those in pigs fed the HFS diet. AID and SID of glutamic acid were higher in pigs fed HML and FPBM diets. Conclusion: In conclusion, dietary supplementation of mealworm larvae hydrolysate had higher digestibility in DM, CP, Lys, Met, and Thr compared to dietary supplementation with fermented poultry by-product and hydrolyzed fish soluble.Y

A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate

Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice

SCOPE: Ginger exerts protective effects on obesity and its complications. Our objectives here are to identify bioactive compounds that inhibit adipogenesis and lipid accumulation in vitro, elucidate the anti-obesity effect of gingerenone A (GA) in diet-induced obesity (DIO), and investigate whether GA affects adipose tissue inflammation (ATI). METHODS AND RESULTS: Oil red O staining showed that GA had the most potent inhibitory effect on adipogenesis and lipid accumulation in 3T3-L1 cells among ginger components tested at a single concentration (40 muM). Consistent with in vitro data, GA attenuates DIO by reducing fat mass in mice. This was accompanied by a modulation of fatty acid metabolism via activation of AMP-activated protein kinase (AMPK) in vitro and in vivo. Additionally, GA suppressed ATI by inhibiting macrophage recruitment and downregulating pro-inflammatory cytokines. CONCLUSION: These results suggest that GA may be used as a potential therapeutic candidate for the treatment of obesity and its complications by suppressing adipose expansion and inflammation

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC