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




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BMC Cancer

, 11:158

Cell and molecular biology

Abstract

BackgroundSome 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.

MethodsMigration 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.

ResultsHypoxia 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.

ConclusionsHypoxia 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.

List of abbreviationsCAcarbonic anhydrase

CKcytokeratin

CMconditioned medium

EMTepithelial-mesenchymal transition

ERoestrogen receptor

G-CSFgranulocyte-colony stimulating factor

HIFhypoxia-inducible factor

IFNinterferon

IPIFN-γ inducible protein

MCPmonocyte chemoattractant protein

MIGmonokine induced by IFN-γ

MIPmacrophage inflammatory protein

NGneutrophil granulocytes

NGFnerve growth factor

PGRprogesterone receptor

PMSphenazine methosulphate

RANTES regulated on activationnormal T-cell expressed and secreted

TNFtumor necrosis factor

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-11-158 contains supplementary material, which is available to authorized users.

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Author: Melanie J Voss - Mischa F Möller - Desmond G Powe - Bernd Niggemann - Kurt S Zänker - Frank Entschladen

Source: https://link.springer.com/







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