SummaryPrevious studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.

A lowenergy electron diffraction data acquisition system for very low electron doses based upon a slow scan charge coupled device camera Rev.Irradiating molecularly adsorbed NH 3 with controlled fluences of 50 eV electrons on Pt͑111͒ at 100 K leads to NH 2 , NH, and H species. Temperature programmed desorption shows dihydrogen desorption, confirming electron induced decomposition of ammonia, and a new NH 3 desorption peak ͑210 K͒ attributed to hydrogenation of NH 2 . High resolution electron energy loss spectroscopy identifies NH 2 through two vibrational features at 830 and 1392 cm Ϫ1 that are assigned to rocking and wagging modes, and NH through a single strong stretching feature at 3280 cm Ϫ1 . NH was stable up to 400 K where it dehydrogenated, leaving N on the surface, which was stable up to 700 K. In x-ray photoelectron spectroscopy a N(1s) peak, shifted to lower binding energy, appears after electron irradiation.

Twenty six of 28 species of snappers (Lutjanidae), examined for dactylogyrids (Monogenoidea) from the Red Sea, the Indo-west and eastern Pacific Ocean, the Gulf of Mexico and the Caribbean Sea, were infected: 18 species with Euryhaliotrema spp., 17 with species of Haliotrematoides n. gen. and eight with species of undetermined dactylogyrid genera. Two species of fusiliers (Caesionidae) and one species of porgy (Sparidae) were also examined and found positive for species of Haliotrematoides. Haliotrematoides n. gen., supported by both 18S rDNA and 28S rDNA analyses, was proposed for 15 new and 15 previously described species of Haliotrema (s. l.) from lutjanid, caesionid and sparid hosts: Haliotrematoides hatzenbuehlerae n. sp., Haliotrematoides brachyflagellocirrus n. comb., Haliotrematoides caesionis n. comb., Haliotrematoides calcaris n. comb., Haliotrematoides cornigerum n. comb., Haliotrematoides gracilihamus n. comb., Haliotrematoides guttati n. comb., Haliotrematoides heteracantha n. comb., Haliotrematoides isolens n. sp., Haliotrematoides lanx n. sp., Haliotrematoides longihamus n. comb., Haliotrematoides longitubocirrus n. comb., Haliotrematoides magnigastrohamus n. comb., Haliotrematoides mastigion n. sp., Haliotrematoides mediohamides n. sp., Haliotrematoides mediohamus n. comb., Haliotrematoides nagibinae n. sp., Haliotrematoides noncalcaris n. comb., Haliotrematoides noncalcaroides n. sp., Haliotrematoides novaecaledoniae n. sp., Haliotrematoides overstreeti n. sp., Haliotrematoides parvicirrus n. comb., Haliotrematoides patellacirrus n. comb., Haliotrematoides plectridium n. sp., Haliotrematoides potens n. sp., Haliotrematoides prolixohamus n. sp., Haliotrematoides shenzhenensis n. comb., Haliotrematoides spinatus n. sp., Haliotrematoides tainophallus n. sp., Haliotrematoides zhukovi n. sp. The new genus was characterized by dactylogyrids having 1) an unique hook distribution with pairs 1, 2, 3, 7 on the peduncle or trunk of the body, pair 5 associated with the point and distal shaft of the ventral anchors, and pairs 4 and 6 located at the level of the anchor bases or shifted anteriorly to the union of the haptor and peduncle; 2) dorsal anchors lacking well-developed deep roots and having perforated bases, elongate relatively straight shafts, and superficial grooves on the distal portions of the shafts and/or points; 3) ventral anchors with developed basal roots, an elongate shaft, and superficial grooves along the distal portions of the shafts and/or points; 4) a ventral bar usually with two submedial pockets along the anterior margin; and 5) a copulatory complex lacking an accessory piece. New host and locality records for some previously described species were reported.

The S100 protein family member S100A4 regulates various cellular functions. Previous studies have shown that elevated expression of S100A4 is associated with progression and metastasis of colorectal cancer (CRC). However, little is known about whether and how S100A4 contributes to CRC development. In our present study, the elevated expression of S100A4 in CRC tissues compared to matched adjacent normal tissues was confirmed by immunohistochemistry, semi-quantitative RT-PCR and Western blot. Adenovirus-mediated S100A4 overexpression obviously enhanced viability and migration of CRC cells, which was detected by MTT assay and transwell assay, respectively. Additionally, S100A4 overexpression increased the phosphorylation levels of Akt, mTOR and p70S6K. These effects of S100A4 were abolished by treatment with either the specific PI3K/Akt inhibitor LY294002, or the specific mTOR/p70S6K inhibitor rapamycin. Furthermore, overexpression of S100A4 resulted in upregulation of VEGF and downregulation of E-cadherin, which were strongly reversed by either LY294002 or rapamycin. Altogether, our results demonstrate that activation of the PI3K/Akt/mTOR/p70S6K signaling pathway is involved in S100A4-induced viability, migration, upregulation of VEGF and downregulation of E-cadherin in CRC cells.

The S100A6 protein, a member of the S100 protein family, is overexpressed in many tumors including colorectal carcinoma (CRC). Although recent studies showed that the elevated expression of S100A6 was associated with the stage and lymphatic permeation of CRC, little is known about whether and how S100A6 contributes to CRC development. Here we investigated the S100A6 expression in CRC tissues and cell lines, and explored the molecular mechanisms underlying the role of S100A6 in CRC development by examining cell proliferation and migration in vitro, and tumorigenicity in nude mice. The results show that S100A6 expression was markedly increased in CRC tissues and cell lines compared to normal colon tissues and a normal colon mucosal epithelial cell line, respectively. Recombinant adenovirus-mediated overexpression of S100A6 or treatment with recombinant S100A6 protein in HCT116, a CRC cell line with relative low S100A6 expression, resulted in enhanced cell proliferation and migration, and the mitogen-activated protein kinase (MAPK) activation in vitro, and tumor growth in vivo. Conversely, RNAi-mediated knockdown of S100A6 in LoVo, a CRC cell line with relative high S100A6 expression, resulted in reduced cell proliferation, migration and MAPK activity. S100A6-induced proliferation was partially attenuated by an ERK inhibitor while migration was suppressed by a p38 inhibitor. Taken together, our results suggest that the cellular effects of S100A6 are mediated by the ERK and p38 MAPK pathways, and modulation of these pathways may be employed for CRC prevention and therapy.