The effect of Vasohibin-1 expression and tumor-associated macrophages on the angiogenesis in vitro and in vivo

Peer reviewe

Increasing the Inflammatory Competence of Macrophages with IL-6 or with Combination of IL-4 and LPS Restrains the Invasiveness of Pancreatic Cancer Cells

Recent studies suggest that pro-inflammatory type M1 macrophages inhibit tumor progression and that anti-inflammatory M2 macrophages enhance it. The aim of this study was to examine the interaction of type M1 and M2 macrophages with pancreatic cancer cells. We studied the migration rate of fluorescein stained pancreatic cancer cells on Matrigel cultured alone or with Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) differentiated macrophages or with Macrophage Colony Stimulating Factor (M-CSF) differentiated macrophages, skewing the phenotype towards pro- and anti-inflammatory direction, respectively. Macrophage differentiation was assessed with flow cytometry and the cytokine secretion in cell cultures with cytokine array. Both GM-CSF and M-CSF differentiated macrophages increased the migration rate of primary pancreatic adenocarcinoma cell line (MiaPaCa-2) and metastatic cell line (HPAF-II). Stimulation with IL6 or IL4+ LPS reversed the macrophages' increasing effect on the migration rate of Mi-aPaCa-2 completely and partly of HPAF-II. Co-culture with MiaPaCa-2 reduced the inflammatory cytokine secretion of GM-CSF differentiated macrophages. Co-culture of macrophages with pancreatic cancer cells seem to change the inflammatory cytokine profile of GM-CSF differentiated macrophages and this might explain why also GM-CSF differentiated macrophages promoted the invasion. Adding IL6 or IL4+ LPS to the cell culture with MiaPaCa-2 and GM-CSF or M-CSF differentiated macrophages increased the secretion of inflammatory cytokines and this could contribute to the reversion of the macrophage induced increase of cancer cell migration rate.Peer reviewe

Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGF beta 2/NF-kappa B/Kindlin-2 axis

Objective: Recent studies have shown that tumor-associated macrophages (TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer (GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified. Methods: THP-1 monocytes were induced by PMA/interleukin (IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation (ChIP) assay were used to investigate the mechanism of transforming growth factor beta 2 (TGF beta 2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo. Results: We found that Kindlin-2 expression was upregulated at both mRNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGF beta 2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-kappa B. TAMs thus participated in the progression of GC through the TGF beta 2/NF-kappa B/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo. Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGF beta 2/NF-kappa B/Kindlin-2 axis, providing a possibility for new treatment options and approaches.Peer reviewe

Tumour-associated macrophages activate migration and STAT3 in pancreatic ductal adenocarcinoma cells in co-cultures

Objectives: Tumour-associated macrophages participate in tumour development and progression. The aim of this study was to assess the interactions of pancreatic cancer cells and pro-inflammatory M1 and anti-inflammatory M2 macrophages, specifically their effect on pancreatic cancer cell migration and the changes in STAT-signalling. Methods: Monocytes were isolated from healthy subjects and differentiated into macrophages with M-CSF. The macrophages were polarized towards M1 by IL-12 and towards M2 by IL-10. We studied also the effect of pan-JAK/STAT-inhibitor P6. Macrophage polarization and STAT and NF kappa B-activation in both MiaPaCa-2 and macrophages were assessed by flow cytometry. We recorded the effect of co-culture on migration rate of pancreatic cancer cells MiaPaCa-2. Results: Macrophages increased the migration rate of pancreatic cancer cells. Co-culture activated STAT1, STAT3, STAT5, AKT and NF kappa B in macrophages and STAT3 in MiaPaCa-2 cells. IL-12 polarized macrophages towards M1 and decreased the migration rate of pancreatic cancer cells in co-cultures as well as P6. IL-10 skewed macrophage polarization towards M2 and induced increase of pancreatic cancer cells in co-cultures. Conclusion: Co-culture with macrophages increased pancreatic cancer cell migration and activated STAT3. It is possible to activate and deactivate migration of pancreatic cancer cells trough macrophage polarization. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.Peer reviewe

Robust Fusion of Diffusion MRI Data for Template Construction

Abstract Construction of brain templates is generally carried out using a two-step procedure involving registering a population of images to a common space and then fusing the aligned images to form a template. In practice, image registration is not perfect and simple averaging of the images will blur structures and cause artifacts. In diffusion MRI, this is further complicated by intra-voxel inter-subject differences in fiber orientation, fiber configuration, anisotropy, and diffusivity. In this paper, we propose a method to improve the construction of diffusion MRI templates in light of inter-subject differences. Our method involves a novel q-space (i.e., wavevector space) patch matching mechanism that is incorporated in a mean shift algorithm to seek the most probable signal at each point in q-space. Our method relies on the fact that the mean shift algorithm is a mode seeking algorithm that converges to the mode of a distribution and is hence robust to outliers. Our method is therefore in effect seeking the most probable signal profile at each voxel given a distribution of signal profiles. Experimental results show that our method yields diffusion MRI templates with cleaner fiber orientations and less artifacts caused by inter-subject differences in fiber orientation

Image mosaicking using SURF features of line segments

<div><p>In this paper, we present a novel image mosaicking method that is based on Speeded-Up Robust Features (SURF) of line segments, aiming to achieve robustness to incident scaling, rotation, change in illumination, and significant affine distortion between images in a panoramic series. Our method involves 1) using a SURF detection operator to locate feature points; 2) rough matching using SURF features of directed line segments constructed via the feature points; and 3) eliminating incorrectly matched pairs using RANSAC (RANdom SAmple Consensus). Experimental results confirm that our method results in high-quality panoramic mosaics that are superior to state-of-the-art methods.</p></div

Matching by different methods.

<p>(A) SURF, (B) SIFT, (C) Our method.</p

Mosaicking results given by our method.

<p>Mosaicking results given by our method.</p

Image pairs with photometric or geometric variations.

<p>(A) lighting, (B) rotation, (C) blur, (D) scaling. Reprinted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173627#pone.0173627.ref030" target="_blank">30</a>] under a CC BY license, with permission from [Computational and Mathematical Methods in Medicine], original copyright [2014].</p