Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential

Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10−/− mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells

Les Macroalgues de la Côte d'Opale : un siècle d'inventaires et perspectives actuelles, in Observation des écosystèmes marin et terrestre de la Côte d'Opale : du naturalisme à l'écologie, édité par F.G. Schmitt

L'année 2008 a marqué le centenaire de la mort de d'Alfred Giard, qui a été l'initiateur des recherches et observations sur la côte d'opale, et de l'établissement d'institutions de recherche à Wimereux. Auteur de plusieurs centaines d'articles, il a fait connaître Wimereux à l'étrangerà travers ses travaux. Par ses observations réalisés sur la côte d'opale, il a été le premier à faire connaître cet environnement au sein de la littérature scientifique internationale. Lorsqu'il a fondé la station zoololique de Wimereux en 1874 il s'agissait du quatrième laboratoire maritime ouvert sur les littoraux français, après Concarneau,Marseille et Roscoff. Nous avons organisé en juillet 2008 un coloque international et interdisciplinaire pour marquer le centenaire de la disparition d'Alfred Giard. Une première journée a été consacrée à des aspects historiques liés à l'activite scientifique de Giard : histoire des stations marines, histoire des activités de recherches marines dans le Boulonnais, histoire des théories sur l'évolution. Laseconde journée a été consacrée à l'écologie et observation de l'écosystème de la côte d'opale. Cet article d'introduction rappelle certains faits sur Giard,sur les stations de Wimereux et de la côte d'opale, et sur leur héritage et introduit les autres contribution

A fully automated system for measurements of photosynthetic oxygen exchange under immersed conditions: an example of its use in Laminaria digitata (Heterokontophyta: Phaeophyceae)

International audienceA new, fully-automated, closed-chamber system was developed for measuring photosynthetic activity in aquatic plants, algae, or corals during immersion. The performance of this system, which monitors oxygen exchange, was evaluated both in the laboratory and in situ under natural conditions using the seaweed Laminaria digitata. Intact, large individuals were placed inside the chamber and kept in place by a plastic grid in a transparent Perspex dome. The grid separated the upper incubation chamber containing the alga from the detectors that were situated in the lower chamber. Oxygen was measured using a novel method based on lifetime optical fluorescence sensor technology that provides an extremely stable and precise measurement of dissolved oxygen. The circulation and homogenization of the medium between the samples and the detectors in this closed system were provided by two pumps. The medium could be renewed by another pump that opened to the external ambient seawater and controlled by a solenoid valve. All the mechanics were driven by an electronic card that allowed choice of filling time, time of measurement, and time of medium renewal. This system provides a new tool to study, in detail, the photosynthesis of whole aquatic organisms under natural field conditions during immersion, combining high time-resolution of oxygen exchange with a long temporal scale of in situ measurements. By allowing automatic and very accurate measurements without any intervention during monitoring, this system will be useful for estimating and comparing production of primary producers or for assessing the influence of environmental factors on production

In situ photosynthetic performance of Laminaria digitata (Phaeophyceae) during spring tides in Northern Brittany

International audienceThe ability of Laminaria digitata (Hudson) J.V. Lamouroux to cope with rapid and drastic changes in light was studied in the field by measuring photosystem II fluorescence, net oxygen roduction and pigment content. Experiments were conducted during two spring tides of late spring in Northern Brittany where low spring tides occur around noon. Daily patterns of the photosynthetic performance of Laminaria digitata were observed in relation to changes in incident under- water light. Photoinhibitory light exposure induced a sharp decrease of the optimal quantum yield (Fv/Fm), a decline of the net oxygen production in the first of the two spring tides investigated and a concomitant increase in the de-epoxidation ratio of the Violaxanthin pool. Photoinhibition persisted at a lower extent at the end of the day and complete recovery was achieved during the night. The implications of the photoinhibition of photosynthesis of Laminaria digitata are discussed in relation to the natural ambient conditions experienced in the field

Diatom Frustules Nanostructure in Pelagic and Benthic Environments

International audienceDiatoms are an important group of eukaryotic microalgae with a siliceous cell wall, the frustule. Diatoms are traditionally subdivided into two sub-classes, namely centric diatoms with a radial symmetry and pennate diatoms with a bilateral symmetry. These two groups of diatoms have usually biotope preferences, with centric diatoms dominating the pelagic environments, whereas the benthic habitats are mostly inhabited by pennate diatoms. The question of how the morphology of diatoms (centric versus pennate) or the ultrastructure of the frustule could be driven by ecological constrains remains unclear. For example, some studies have suggested that the structure of the diatom frustule could play a role in the light harvesting performances. In this work, we studied the variations of the diatom frustules nanostructure in several benthic and pelagic species inhabiting the same coastal ecosystem, particularly the ultrastructure that includes the distribution and size of the frustule pores. Although the species studied here experience different ecological constrains in term of light, we found no significant differences between benthic and pelagic species, in either the size of the pores (average =285 (+/- 108) nm) or the distance between them (average =234 (+/- 87) nm). Moreover, the intra-species variability was sometimes larger than the variability observed between cells from different genera. We concluded that the pore morphometry is controlled by a combination of genetically-driven processes of bio-mineralization, and episodic variations in environmental growth conditions which influence the chemical precipitation of silica within the cells