Macrophage coculture enhanced invasion of gastric cancer cells via TGF-β and BMP pathways

Abstract

Objective. Transforming growth factor β (TGF-β) superfamily plays an important role in regulating gastric cancer progression. As previously demonstrated, tumor-associated macrophages (TAMs) promoted the invasion of gastric cancer cells in Matrigel. However, the role of TGF-β superfamily signaling between TAMs and gastric cancer remains unclear. Material and methods. Three-dimensional dynamic migration imaging system was used to detect gastric cancer invasion rate cocultured with macrophages in Matrigel before or after TGF-β receptor 1 or bone morphogenic protein (BMP) receptor 1A and 1B inhibition; real-time RT-PCR was used to quantitatively investigate gene expression (TGF-β1, TGF-β2, BMP4, and BMP7, ADAM9, MMP9, TIMP3, VEGF-A, and VEGF-C). Results. TGF-β1, TGF-β2, BMP4, and BMP7 expressions were increased significantly in macrophages grown with cancer cells as compared to macrophages grown alone. The invasion rate and invasion-related genes expressions of both AGS and Hs-746T gastric cancer cell lines were upregulated by macrophages, although the expression profile was different. Invasion rate and invasion-related genes' expressions of AGS cells cocultured with macrophages were downregulated significantly after TGF-βR1 and BMPR1 inhibition. Conclusions. Macrophages associated with tumor might promote gastric cancer cells invasion though enhancing TGF-β/BMPs signal pathway. Inhibiting TGF-β/BMPs signal between TAMs and gastric cancer cells might provide a new therapeutic method of gastric cancer.     

Expression of CD105 and CD34 receptors controls BMP‐induced in vitro mineralization of mouse adipose‐derived stem cells but does not predict their in vivo bone‐forming potential

Adipose‐derived stem cells (ADSCs) can be excellent alternative to bone marrow derived stem cells for enhancing fracture repair since ADSCs can be isolated comparatively in large numbers from discarded lipoaspirates. However, osteogenic potential of ADSCs in vivo is very controversial. We hypothesized that adipose‐derived stem cells (ADSCs) that respond maximally to bone morphogenetic proteins (BMPs) in vitro would possess maximum bone‐forming potential. Four purified populations of mouse ADSCs: CD105⁺CD34⁺, CD105^?CD34^?, CD105⁺CD34^? and CD105^?CD34⁺ were obtained using fluorescence‐activated cell sorting (FACS) and their BMP‐responsiveness was determined in vitro. CD105⁺CD34^? population showed the strongest response to BMPs in terms of robust increase in mineralization. Expression of CD105 correlated with high BMP‐responsive phenotype and larger cell size while expression of CD34 correlated with low BMP‐responsive phenotype and smaller cell size. CD105⁺CD34^? population displayed higher gene expression of Alk1 or Alk6 receptors in comparison with other populations. However, CD105⁺CD34^? ADSCs failed to induce ectopic bone formation in vivo after they were transplanted into syngeneic mice, indicating that in vitro BMP‐responsiveness is not a good indicator to predict in vivo bone forming potential of ADSCs. Therefore greater precautions should be executed during selection of competent ADSCs for bone repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:625–632, 2015.

     

骨形成蛋白及其mRNA在成釉细胞瘤中的表达

目的：检测成釉细胞瘤中的ＢＭＰ的表达,探讨成釉细胞瘤的发生及病理机理。方法：采用免疫组化和原位杂交的方法,检测２４例成釉细胞瘤标本中ＢＭＰ蛋白和ＢＭＰ－２、－４ｍＲＮＡ表达。结果：成釉细胞瘤中的柱状上皮层和星网状细胞层中均有ＢＭＰ－２、－４ｍＲＮＡ和ＢＭＰ蛋白的表达,ＢＭＰ－２、－４ｍＲＮＡ的杂交信号强度在柱状上皮层小于星网状细胞。结论：ＢＭＰ的表达为探讨成釉细胞瘤的来源提供了分子基础;ＢＭＰ可能参与了肿瘤病理机理及生物学行为的形成。     

Evaluating acute toxicity of methyl parathion application in constructed wetland mesocosms

Wetland ecosystems have reduced ambient levels of various organic and metallic compounds, although their effectiveness on agricultural pesticides is not well documented. Five stations within each of two 10 x 50 m constructed wetlands (two vegetated, two nonvegetated) were selected to measure the fate and effects of methyl parathion (MeP). Following a simulated storm event (0.64 cm of rainfall), aqueous, sediment, and plant samples were collected and analyzed spatially (5, 10, 20, and 40 m from the inlet) and temporally (after 3-10 days) for MeP concentrations and for the impact of those concentrations on the aquatic fauna. Aqueous toxicity to fish decreased spatially and temporally in the vegetated mesocosm. Pimephales promelas survival was significantly reduced, to 68%, at the 10-m station of the nonvegetated wetlands (3 h postapplication), with pesticide concentrations averaging 9.6 microg MeP/L. Ceriodaphnia in both the vegetated and nonvegetated wetlands was sensitive (i.e., a significant acute response to MeP occurred) to pesticide concentrations through 10 days postapplication. Mean MeP concentrations in water ranged from 0.5 to 15.4 microg/L and from 0.1 to 27.0 microg/L in the vegetated and nonvegetated wetlands, respectively. Hyalella azteca aqueous tests resulted in significant mortality in the 5-m vegetated segment 10 days after exposure to MeP (2.2 microg/L). Solid-phase (10-day) sediment toxicity tests showed no significant reduction in Chironomus tentans survival or growth, except for the sediments sampled 3 h postapplication in the nonvegetated wetland (65% survival). Thereafter, midge survival averaged >87% in sediments sampled from both wetlands. These data suggest that wetlands play a significant role in mitigating the effect of MeP exposure in sensitive aquatic biota.     

骨形成蛋白—2／4、—5及Ⅰ型、Ⅱ型BMP受体在舌癌细胞系Tca8113细胞中的表达及意义

目的 探讨骨形成蛋白（BMP）及其受体与口腔鳞癌发生、发展的可能关系。方法 用免疫组织化学、原位杂交方法分析BMP－2／4、－5及Ⅰ型、Ⅱ型BMP受体在Tac8113细胞中的表达。结果Tca8113细胞能不同程度表达BMP－2／4、－5及Ⅰ、Ⅱ型BMP受体，其阳性信号定位于癌细胞胞浆。结论 BMP及其受体与口腔鳞癌发生、发展有密切关系。     

菌源性磁珠在病原菌检测中的应用

目的 建立一种可检测低浓度大肠埃希菌O157等的产Vero毒素大肠埃希菌（verotoxigenic escherichia coli,VTEC）的方法.方法 从磁性细菌中获取菌源性磁珠（bacterial magnetic particles,BMPs）,将大肠埃希菌O157抗体接种于BMPs表面,形成免疫BMPs.收集养牛场排出的污水标本,每份10ml中添加免疫BMPs 1mg,通过外磁场诱导,以免疫BMPs对污水标本进行靶向取样.增菌培养12h,以VTEC的vt1（Vero毒素1基因）、vt2（Vero毒素2基因）为增扩对象,进行PCR检测.作为对照,同样的污水标本,每份10ml,常规离心分离,分离物经过12h增菌培养后,同样进行PCR检测.结果 经免疫BMPs靶向取样处理后,40份污水标本,确诊含有vt1及/或vt2基因的6份.而同样40份污水标本,经离心分离处理,最后确诊含有vt1和/或vt2基因的1份.结论 对于有大量杂菌和异物的污水标本,利用免疫BMPs,通过外磁场诱导可对目标病原菌进行靶向取样,作为病原菌检测的辅助手段,可降低漏检率.     

Innovations in osteosynthesis and fracture care

Over the years giant steps have been made in the evolution of fracture fixation and the overall clinical care of patients. Better understanding of the physiological response to injury, bone biology, biomechanics and implants has led to early mobilisation of patients. A significant reduction in complications during the pre-operative and post-operative phases has also been observed, producing better functional results. A number of innovations have contributed to these improved outcomes and this article reports on the advances made in osteosynthesis and fracture care.