Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

<p>Abstract</p> <p>Background</p> <p>Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines.</p> <p>Methods</p> <p>Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested.</p> <p>Results</p> <p>Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration.</p> <p>Conclusions</p> <p>Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients.</p

MULTI-LEVEL POLICY COALITIONS AN INTERPRETATIVE MODEL OF WATER CONFLICTS IN THE AMERICAS

ABSTRACT This article proposes an analytical approach to conflicts and policy-making related to urban water management based on multi-level policy coalitions. This is necessary to articulate four main issues. First, the repositioning of social and political struggles for access to water, along with policy variables. Second, the analysis of the effects of ecological transition, including climate change. Third, the reincorporation of these struggles and challenges in a multi-level approach. Finally, the enquiry into the apparent contradiction, in contemporary policymaking. The article proposes a definition of multi-level coalitions as collective preference systems that influence the content of policies (ideas/advocacy, decisions, policy tools) and their implementation, groups of actors that arise from engagement in policy issues. In the first section, the article presents the objectives of research on urban water management in the Americas, within the framework of which this analytical approach by multi-level coalitions is fashioned. In the second section, the article details four analytical issues. In the third section, it gives a definition of multi-level coalitions