32 research outputs found

    Subclonal cooperation rewrites metastasis

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    Sewn boats in the Qatar Museums collection, Doha: baggāras and kettuvallams as records of a Western Indian Ocean technological tradition

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    This is the final version. Available on open access from Wiley via the DOI in this recordVernacular sewn boats from southern Iran and Kerala, India, in the collection of Qatar Museums are documented and their construction described. The Iranian baggāras are unique preservations of sewn boats from the Arabian-Persian Gulf, notable for their previously undocumented keel-garboard sewing technique and extensive use of bitumen coatings. Comparison between individual boats enable conclusions to be drawn about the builders’ conception, as well as variation within the type. The Keralite kettuvallams represent an ongoing vernacular tradition that is nevertheless poorly documented or preserved in museum contexts. Construction drawings, naval lines drawings and 3D photogrammetry models are provided for all vessels.University College London-Qatar (UCL-Q)University of ExeterUniversity of Naples ‘l’Oriental

    Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells

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    Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (FEDER funds) PI10/02295 PI10/02149Fundacion Progreso y Salud, Consejeria de Salud, Junta de Andalucia (Ministry of Health, Government of Andalucia) PI-0533-2014Consejeria Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia (Ministry of Economy, Innovation, Science and Employment, Government of Andalucia) CTS-656

    Technical Advancements for Studying Immune Regulation of Disseminated Dormant Cancer Cells

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    Metastases are a major cause of cancer-related death and despite the fact that they have been focus of intense research over the last two decades, effective therapies for patients with distant secondary lesions are still very limited. In addition, in some tumor types metastases can grow years after the patients have been declared clinically cured, indicating that disseminated cancer cells (DCCs) persist undetected for years, even decades in a quiescent state. Clinical and experimental data highlight the importance of the immune system in shaping the fitness and behaviour of DCCs. Here, we review mechanisms of survival, quiescence and outgrowth of DCCs with a special focus on immune-regulation and we highlight the latest cutting-edge techniques for modelling the biology of DCCs in vitro and for studying the metastatic niche in vivo. We believe that a wide dissemination of those techniques will boost scientific findings towards new therapies to defeat metastatic relapses in cancer patients

    Generation of neighbor-labeling cells to study intercellular interactions in vivo

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    Understanding cell-cell interactions is critical in most, if not all, research fields in biology. Nevertheless, studying intercellular crosstalk in vivo remains a relevant challenge, due mainly to the difficulty in spatially locating the surroundings of particular cells in the tissue. Cherry-niche is a powerful new method that enables cells expressing a fluorescent protein to label their surrounding cells, facilitating their specific isolation from the whole tissue as live cells. We previously applied Cherry-niche in cancer research to study the tumor microenvironment (TME) in metastasis. Here we describe how to generate cancer cells with the ability to label their neighboring cells (within the tumor niche) by transferring a liposoluble fluorescent protein. Live niche cells can be isolated and compared with cells distant from the tumor bulk, using a variety of ex vivo approaches. As previously shown, this system has the potential to identify novel components in the TME and improve our understanding of their local interactions. Importantly, Cherry-niche can also be applied to study potential cell-cell interactions due to in vivo proximity in research fields beyond cancer. This protocol takes 2-3 weeks to generate the labeling cells and 1-2 weeks to test their labeling ability

    Generation of neighbor-labeling cells to study intercellular interactions in vivo.

    No full text
    Understanding cell-cell interactions is critical in most, if not all, research fields in biology. Nevertheless, studying intercellular crosstalk in vivo remains a relevant challenge, due mainly to the difficulty in spatially locating the surroundings of particular cells in the tissue. Cherry-niche is a powerful new method that enables cells expressing a fluorescent protein to label their surrounding cells, facilitating their specific isolation from the whole tissue as live cells. We previously applied Cherry-niche in cancer research to study the tumor microenvironment (TME) in metastasis. Here we describe how to generate cancer cells with the ability to label their neighboring cells (within the tumor niche) by transferring a liposoluble fluorescent protein. Live niche cells can be isolated and compared with cells distant from the tumor bulk, using a variety of ex vivo approaches. As previously shown, this system has the potential to identify novel components in the TME and improve our understanding of their local interactions. Importantly, Cherry-niche can also be applied to study potential cell-cell interactions due to in vivo proximity in research fields beyond cancer. This protocol takes 2-3 weeks to generate the labeling cells and 1-2 weeks to test their labeling ability

    Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization

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    Radiotherapy is one of the most effective approaches to achieve tumour control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. In this study, we used a model of acute radiation injury to the lung in the context of cancer metastasis, to understand the biological link between tissue damage and cancer progression. We exposed healthy mouse lung tissue to radiation prior to the induction of metastasis and observed a strong enhancement of cancer cell growth. We found that locally activated neutrophils were key drivers of the tumour-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signalling. Importantly, these tissue perturbations endowed arriving cancer cells with an augmented stemness phenotype. By preventing neutrophil-dependent Notch activation, via blocking degranulation, we were able to significantly offset the radiation-enhanced metastases. This work highlights a pro-tumorigenic activity of neutrophils, which is likely linked to their tissue regenerative functions
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