Our study suggests miR-141 is a regulator of brain metastasis from breast cancer and should be examined as a biomarker and potential target to prevent and treat brain metastases.

IntroductionInflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d’orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth.MethodsHypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs).ResultsMSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors.ConclusionsOur findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0549-4) contains supplementary material, which is available to authorized users.

Comparative X-ray structure studies reveal that C-F bond incorporation into the peripheral pyrrolidine moieties of the G-quadruplex DNA binding ligand BSU6039 leads to a distinct pyrrolidine ring conformation, relative to the non-fluorinated analogue, and with a different binding mode involving reversal of the pyrrolidinium N(+)-H orientation.

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