Triple-negative breast cancer (TNBC) can be divided into six subtypes. Among these subtypes, the basal-like 2 (BL2) subtype shows the lowest five-year survival rate and highest risk of metastasis. ...Alpha-crystallin B chains (αB-crystallin), a small heat shock protein that is known
to be involved in breast cancer metastasis, is highly expressed in the basal-like subtype but not in the other non-basal subtypes. Thus, we hypothesized that αB-crystallin may be an important factor involved in the worse prognosis of the BL2 subtype compared with those of the other TNBC
subtypes. Here, we examined the role of αB-crystallin in cell motility in two TNBC cell lines: HCC1806 (BL2 subtype) and, as control, MDA-MB-436 (mesenchymal stem-like subtype). HCC1806 showed greater cell migration capacity and a higher expression level of the gene encoding αB-crystallin
(CRYAB) than did MDA-MB-436. Short interfering RNA-mediated silencing of CRYAB expression significantly reduced the cell migration capacity of HCC1806 cells, whereas it had no effect in MDA-MB-436 cells, indicating that αB-crystallin is essential for the migration
of HCC1806 cells. Thus, high αB-crystallin expression may be a contributing factor to the poor prognosis of BL2 TNBC.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a favorable treatment outcome in patients with EGFR mutation-positive non-small cell lung cancer. However, most of such ...patients become resistant to EGFR-TKIs within a year. Thus, clarifying the mechanism
of acquired resistance to EGFR-TKIs has been a research focus. Here, we demonstrated that the expression of progesterone receptor membrane component 2 (PGRMC2) was upregulated in an erlotinib-resistant cell line, PC9/ER, compared with the parental PC9 lung cancer cells. Our previous study
showed that PGRMC1 is responsible for acquired resistance to erlotinib; however, PGRMC2 has not been discussed yet. Thus, the aim of this study was to determine the role of PGRMC2 in acquired resistance to erlotinib. Transfection with PGRMC2 siRNA significantly enhanced the sensitivity to
erlotinib in PC9/ER cells. Furthermore, knockdown of PGRMC2 reduced the expression of p21, which is known as cell-cycle inhibitor and antiproliferative effector. These results suggest that PGRMC2 partially contributes to erlotinib resistance in PC9/ER cells, and that investigation into the
effect of PGRMC2 on apoptosis and the cell cycle are warranted.
Exosomes are potent players in the development of metastases and they play an important role in cancer angiogenesis and exacerbation. However, it is unclear how proteins on exosomes affect ...development of blood vessel networks. In this study, we focused on relationships between membrane
proteins on exosomes and angiogenesis using human umbilical vein endothelial cells (HUVEC). Lung tumor cell-derived exosomes induced tube formation and growth of endothelial cells in vitro in a dose-dependent manner involving MAPK activation, but this was not seen in normal lung epithelial
cells. Ephrin type-A receptor 2 (EphA2) was identified by proteomic analysis and an inhibition assays showed it is a major MAPK activator on exosomes. Thus EphA2 on exosomes participates in angiogenesis as a ligand of the ephrin signaling pathway. These results support the development of novel
therapeutic strategies such as blockade of remote cancer communications through exosomes.
Summary
Background
The relationship among natural allergen exposure, induction of blocking antibody and the occurrence of atopic allergy—particularly in the presence of IgE production—is debatable.
...Objective
To clarify the relationship between the dose of cutaneous exposure to dust mite allergen and susceptibility to the IgE‐mediated allergic response in relation to IgG production.
Methods
NC/Nga mice were epicutaneously exposed to various doses of Dermatophagoides pteronyssinus allergen to induce atopic dermatitis–like skin lesions. We then evaluated the skin lesions, induction of mite‐specific immune responses, and susceptibility to anaphylaxis.
Results
Dose‐dependent exacerbation of atopic dermatitis–like skin lesions and increases in mite‐specific IgG and IgE production were observed. However, mice exposed to relatively low doses of mite allergen showed hypersusceptibility to mite allergen–specific anaphylaxis. We also showed that adoptive transfer of total IgG from Dp‐sensitized mice rescued mice from the hypersusceptibility seen in those exposed to low doses of mite allergen.
Conclusions and Clinical Relevance
High‐dose cutaneous exposure to dust mites induced effective blocking IgG production, even if accompanied by IgE production. Our data might support the concept that an increase in IgG titre, not a decrease in IgE titre, is a marker of clinical improvement in allergen‐specific immunotherapy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
