Asthma-related inflammation promotes lung metastasis of breast cancer cells through CCL11–CCR3 pathway

Background: Mechanisms that preclude lung metastasis are still barely understood. The possible consequences of allergic airways inflammation on cancer dissemination were studied in a mouse model of breast cancer. Methods: Balb/c mice were immunized and daily exposed to ovalbumin (OVA) from day 21. They were subcutane- ously injected with 4T1 mammary tumor cells on day 45 and sacrificed on day 67. Lung metastases were measured by biophotonic imaging (IVIS 200 Imaging System) and histological measurement of tumor area (Cytomine software). Effects of CCL11 were assessed in vivo by intratracheal instillations of recCCL11 and in vitro using Boyden chambers. CCR3 expression on cell surface was assessed by flow cytometry. Results: The extent of tumor metastases was significantly higher in lungs of OVA-exposed mice and increased levels of CCL11 expression were measured after OVA exposure. Migration of 4T1 cells and neutrophils was stimulated in vitro and in vivo by recCCL11. 4T1 cells and neutrophils express CCR3 as shown by flow cytometry and a selective CCR3 antagonist (SB-297006) inhibited the induction of 4T1 cells migration and proliferation in response to recCCL11. Conclusions: Allergic inflammation generated by exposure to allergens triggers the implantation of metastatic cells from primary breast tumor into lung tissues plausibly in a CCL11–CCR3-dependent manner. This indicates that asthma related inflammation in lungs might be a risk factor for lung metastasis in breast cancer patients.Peer reviewe

Emerging Roles of ADAM and ADAMTS Metalloproteinases in Cancer

A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions

Soluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.

peer reviewedEpithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread

Diffusion MRI for following tumor modifications after neoadjuvant radiotherapy.

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and tumor resection in many cancers. The timing between the end of the NeoRT and surgery is driven by the occurrence of side effects or the tumor downsizing. Some studies demonstrated that the timing of surgery and the RT schedule could influence tumor dissemination and subsequently patient overall survival. We demonstrated the impact of NeoRT on metastatic spreading in a Scid mice model. After an irradiation of 2x5gy, we show more metastasis in the lung when the mice are operated at day 4 compared to day 11. Here, our aim is to evaluate with functional MRI (fMRI) the impact of the radiation treatment on the tumor microenvironment and subsequently to identify non-invasive markers helping to determine the best timing to perform surgery for avoiding tumor spreading

Tumor modifications recorded with IVIM and DCE-MRI after Neoadjuvant radiotherapy.

Purpose or Objective Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. We hypothesized anti-cancer treatments (i.e. radiotherapy) modify tumor microenvironment and could potentially impact distant metastases occurrence. Previously, we developed a pre-clinical model demonstrating an impact of NeoRT schedule and the timing of surgery on metastatic spreading (Leroi et al. Oncotarget 2015). Here, we aim to identify by fMRI noninvasive markers reflecting NeoRT related tumor microenvironment modifications that could predict the best timing for performing surgery and avoiding tumor spreading. Material and Methods To briefly delineate the NeoRT model, MDA-MB 231 tumor cells implanted in the flank of SCID mice were locally irradiated with 2x5Gy when tumor reached 100mm3 and then surgically removed at different time points. We performed fMRI, Diffusion Weighted (DW) and Dynamic Contract enhancement (DCE) – MRI, before RT and every 2 days between RT and surgery. We acquired 8 slices of 1 mm thickness and 0.5 mm gap with an “in plane voxel resolution” of 0.5 mm. For DW-MRI, we performed FSEMS (Fast Spin Echo MultiSlice) sequences, with 9 different Bvalue (from 40 to 1000) and B0. We performed IVIM (IntraVoxel Incoherent Motion) analysis to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. For DCE-MRI, we performed a T1 mapping with multiple TR and DCE acquisition with 200 repetitions of 3 sec each and gadolinium IV injection after 10 repetitions. We performed semi-quantitative analysis. We validated tumor perfusion by immunochemistry with injection of FITC-dextran IV 3 min before surgery and CD31 labelling. Human Ki67 was used for lung metastases labelling and quantification. Results After the tumor irradiation, we observed a significant and transient increase at day 6 (60% of the basal value (n=6, p<0,05)) of F and D* parameters related to perfusion. The other parameters of the DW-MRI, ADC and D presented no modifications. The sham irradiated tumors used as control showed no modifications of all fMRI parameters. At the same timing, 6 days post-radiotherapy, DCE-MRI significantly demonstrated a WhashinSlope (n=13, p<0,05) increase. Immunochemistry confirmed the increase of tumor perfusion when surgery is performed at day 6. The sham irradiated tumors never demonstrated such changes. Finally, when surgery is performed on tumor increased perfusion measured by fMRI, it demonstrated a burst of lung metastasis compared to the other timings. Conclusion We showed a significant difference in perfusion-related parameters with fMRI and immunochemistry at a specific time point after NeoRT. These modifications are correlated with an increase of metastasis spreading related to surgery procedure. These results open new perspectives in the personalized medicine and MRI guided surgery timing after NeoRT

Agroecosystem management and biotic interactions: a review

Increasing the use of synthetic fertilisers and pesticides in agroecosystems has led to higher crop yields, accompanied by a decline in biodiversity at the levels of field, cropping system and farm. Biodiversity decline has been favoured by changes at landscape level such as regional farm specialisation, increases in field size, and the removal of hedgerows and woodlots. The loss of biodiversity in agroecosystems has increased the need for external inputs because beneficial functions are no longer provided by beneficial species as natural enemies of crop pests and ecosystem engineers. This trend has led to a strong reliance on petrochemicals in agroecosystems. However, many scientists have been arguing for more than two decades that this reliance on petrochemicals could be considerably reduced by a better use of biotic interactions. This article reviewsoptions to increase beneficial biotic interactions in agroecosystems and to improve pest management and crop nutrition whilst decreasing petrochemical use. Four agronomic options are presented. First, it has been shown that the choice of cultivar, the sowing date and nitrogen fertilisation practices can be manipulated to prevent interactions between pests and crop, in either time or space. Nevertheless, the efficacy of these manipulations may be limited by pest adaptation. Second, beneficial biotic interactions may result from appropriate changes to the habitats of natural enemies and ecosystem engineers, mediated by soil and weed management. Here, knowledge is scarce, and indirect and complex effects are poorly understood. Third, changes achieved by crop diversification and, fourth, by landscape adaptation are promising. However, these practices also present drawbacks that may not necessarily be outweighed by beneficial effects. Overall, these four management approaches provide a powerful framework to develop sustainable agronomic practices

GASCON : Gestion agro-écologique de la santé des cultures et des organismes nuisibles

Le croisement des sciences agronomiques, de l’écologie appliquée à la gestion des agroécosystèmes,et des sciences humaines et sociales, qu’implique la transition agroécologique, pose de nouveaux défis pour répondre aux enjeux agricoles: intégrer des connaissances de différentes disciplines et produites à différentes échelles d’organisation pour agir en situation; développer des cadres d’analyse et démarches intégrant la diversité de situations à gérer par les acteurs et permettant de construire des réponses adaptées à chaque situation; et concevoir et mettre en œuvre des pratiques d’enseignement et d’apprentissage, qui dotent les apprenants de capacités à penser leur action en contexte, en mobilisant des savoirs et savoir-faire multiples en termes de contenus disciplinaires et des savoir-être pour construire des solutions avec une diversité d’acteurs. Dans le champ de la formation, ces défis nécessitent dès lors de revisiter les contenus des enseignements dispensés, les modalités pédagogiques et les dispositifs de formation existants, de manière à appréhender au mieux la complexité des processus à l’œuvre. Pour autant, peu de travaux s’attardent sur les modalités pratiques de ce changement et de ses implications, alors même que de nombreuses initiatives en matière de pédagogie et d’agroécologie se développent ces dernières années. L’objectif de ce séminaire est de promouvoir une information partagée et l’échange d’expériences pour répondre aux enjeux posés par l’agroécologie dans la formation (transversalité, pluridisciplinarité, approche systémique, pédagogies actives). Ces enjeux peuvent se décliner suivant plusieurs entrées : les thématiques enseignées (agriculture, élevage, territoire, alimentation, ...); les pratiques et les dispositifs pédagogiques mis en œuvre pour aborder ces questions (enseignement numérique, dispositifs expérimentaux, projets professionnels, référentiels, ...);les publics d’apprenants: élèves, étudiants, professionnels, ..

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe