Basal-like Breast Cancer Cells Induce Phenotypic and Genomic Changes in Macrophages

Basal-like breast cancer (BBC) is an aggressive subtype of breast cancer that has no biologically-targeted therapy. The interactions of BBCs with stromal cells are important determinants of tumor biology, with inflammatory cells playing well-recognized roles in cancer progression. Despite the fact that macrophage-BBC communication is bidirectional, important questions remain about how BBCs affect adjacent immune cells. This study investigated monocyte-to-macrophage differentiation and polarization, and gene expression in response to coculture with basal-like versus luminal breast cancer cells. Changes induced by coculture were compared to changes observed under classical differentiation and polarization conditions. Monocytes (THP-1 cells) exposed to BBC cells in coculture had altered gene expression with upregulation of both M1 and M2 macrophage markers. Two sets of M1 and M2 markers were selected from the PCR profiles and used for dual immunofluorescence staining of BBC versus luminal cocultured THP-1s, and cancer-adjacent, benign tissue sections from patients diagnosed with BBC or luminal breast cancer confirming the differential expression patterns. Relative to luminal breast cancers, BBCs also increased differentiation of monocytes to macrophages and stimulated macrophage migration. Consistent with these changes in cellular phenotype, a distinct pattern of cytokine secretion was evident in macrophage-BBC cocultures, including upregulation of NAP-2, Osteoprotegerin, MIG, MCP-1, MCP-3 and IL-1β. Application of IL-1 receptor antagonist (IL-1RA) to cocultures attenuated BBC-induced macrophage migration. These data contribute to an understanding of the BBC-mediated activation of the stromal immune response, implicating specific cytokines that are differentially expressed in basal-like microenvironments and suggesting plausible targets for modulating immune responses to BBC

Garnierite mineralization from a serpentinite-derived lateritic regolith, Sulawesi Island, Indonesia: Mineralogy, geochemistry and link to hydrologic flow regime

Garnierite represents a significant nickel ore in many lateritic Ni deposits worldwide. To gain a better understanding of its nature and origin, a well-developed garnierite-hosting transect from the Kolonodale area of East Sulawesi, Indonesia, has been investigated using field geology, mineralogy and geochemical data. Garnierite occurs mainly in veins in the lower saprolite of a serpentinite-derived regolith. Mineralogically, it can be determined as an intimate mixture of Ni-rich serpentine-like (lizardite-Nepouite) and talc-like (kerolite-pimelite) phases. Results of EMP analyses indicate that Ni is preferentially enriched in the talc-like phases rather than the serpentine-like phases. A sequential precipitation of mineral phases progressively enriched in Ni and Si to form garnierite during weathering is suggested. The Ni-lizardite (2.63-8.49 wt% Ni) with elevated Fe (4.02-6.44 wt %) may have been inherited from saprolite in a first instance and enriched in Ni by cation exchange processes. Newly precipitated minerals are kerolite-pimelite (7.84-23.54 wt% Ni) and then followed by Ni-free quartz. Minor amount of Nepouite (23.47-28.51 wt% Ni) occur in laths along shrinkage cracks of previously formed minerals, indicating a late stage paragenetic sequence. With emphasis on a hydrologic consideration, indicators of a preferential flow regime are identified in the garnierite-hosting regolith, including: (i) non-uniform pattern of the garnierite field occurrence, (ii) syn-weathering active nature of the garnierite-hosting structures, (iii) close relationship between the garnierite occurrence and vertical FeeMn oxides pipes as well as FeeMn oxides patched areas, and (iv) specific physico-chemical property of the garnierite location with higher organic matter concentrations but lower pH values compared to surroundings. It is proposed that the origin of garnierite is closely linked to a preferential flow of oversaturated solutions through accessible conduits in the regolith. Garnierite features as colloidal nature, high organic matter and low pH are key-parameters in metal transport and deposition

Basal-like Breast Cancer Cells Induce Phenotypic and Genomic Changes in Macrophages

Basal-like breast cancer (BBC) is an aggressive subtype of breast cancer that has no biologically-targeted therapy. The interactions of BBCs with stromal cells are important determinants of tumor biology, with inflammatory cells playing well-recognized roles in cancer progression. Despite the fact that macrophage-BBC communication is bidirectional, important questions remain about how BBCs affect adjacent immune cells. This study investigated monocyte-to-macrophage differentiation and polarization, and gene expression in response to coculture with basal-like versus luminal breast cancer cells. Changes induced by coculture were compared to changes observed under classical differentiation and polarization conditions. Monocytes (THP-1 cells) exposed to BBC cells in coculture had altered gene expression with upregulation of both M1 and M2 macrophage markers. Two sets of M1 and M2 markers were selected from the PCR profiles and used for dual immunofluorescence staining of BBC versus luminal cocultured THP-1s, and cancer-adjacent, benign tissue sections from patients diagnosed with BBC or luminal breast cancer confirming the differential expression patterns. Relative to luminal breast cancers, BBCs also increased differentiation of monocytes to macrophages and stimulated macrophage migration. Consistent with these changes in cellular phenotype, a distinct pattern of cytokine secretion was evident in macrophage-BBC cocultures, including upregulation of NAP-2, Osteoprotegerin, MIG, MCP-1, MCP-3 and IL-1β. Application of IL-1 receptor antagonist (IL-1RA) to cocultures attenuated BBC-induced macrophage migration. These data contribute to an understanding of the BBC-mediated activation of the stromal immune response, implicating specific cytokines that are differentially expressed in basal-like microenvironments and suggesting plausible targets for modulating immune responses to BBC

SINAT E3 Ligases Control the Light-Mediated Stability of the Brassinosteroid-Activated Transcription Factor BES1 in Arabidopsis

10.1016/j.devcel.2017.03.014DEVELOPMENTAL CELL41147-

SINAT E3 Ligases Control the Light-Mediated Stability of the Brassinosteroid-Activated Transcription Factor BES1 in Arabidopsis

© 2017 Elsevier Inc. The plant hormones brassinosteroids (BRs) participate in light-mediated regulation of plant growth, although the underlying mechanisms are far from being fully understood. In addition, the function of the core transcription factor in the BR signaling pathway, BRI1-EMS-SUPPRESSOR 1 (BES1), largely depends on its phosphorylation status and its protein stability, but the regulation of BES1 is not well understood. Here, we report that SINA of Arabidopsis thaliana (SINATs) specifically interact with dephosphorylated BES1 and mediate its ubiquitination and degradation. Our genetic data demonstrated that SINATs inhibit BR signaling in a BES1-dependent manner. Interestingly, we found that the protein levels of SINATs were decreased in the dark and increased in the light, which changed BES1 protein levels accordingly. Thus, our study not only uncovered a new mechanism of BES1 degradation but also provides significant insights into how light conditionally regulates plant growth through controlling accumulation of different forms of BES1