Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line

Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells (CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs were enriched in sphere-forming test and highly expressed CD44⁺CD24⁻. The spheres and CD24⁻ cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice. CD44⁺CD24⁻ cells expressed stem cell markers and differentiated to CD44⁺CD24⁺ cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44⁺CD24⁻ cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44⁺CD24⁻ phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer.     

Collective cell migration of epithelial and mesenchymal cells

Directional cell migration is required for proper embryogenesis, immunity, and healing, and its underpinning regulatory mechanisms are often hijacked during diseases such as chronic inflammations and cancer metastasis. Studies on migratory epithelial tissues have revealed that cells can move as a collective group with shared responsibilities. First thought to be restricted to proper epithelial cell types able to maintain stable cell–cell junctions, the field of collective cell migration is now widening to include cooperative behavior of mesenchymal cells. In this review, we give an overview of the mechanisms driving collective cell migration in epithelial tissues and discuss how mesenchymal cells can cooperate to behave as a collective in the absence of bona fide cell–cell adhesions.     

Common antigenicity between a human thymic epithelial cell product and a thymus-dependent serum factor

Summary Specific immunofluorescence of human thymic epithelial cytoplasm was obtained with antibodies to supernatant of thymic epithelial cultures, and with anti-prealbumin antibodies. These antibodies also reacted with normal serum but not with serum from Di George patients. The data indicates that thymic epithelium and a component of the prealbumin fraction of normal serum share a common antigen believed to be thymic hormone.Acknowledgment. The authors wish to thank Mrs Francine Rivard and Claire Prévost for technical assistance and Dr A.R.C. Dobell for human thymic material. This work was supported by the National Cancer Institute of Canada and the Medical Research Council of Canada.     

Hypoxia and estrogen receptor profile influence the responsiveness of human breast cancer cells to estradiol and antiestrogens

Angiogenesis activation mediated by vascular endothelial growth factor (VEGF) is one of the factors that can cause antiestrogen treatment failure in estrogen receptor (ER)?positive breast cancer patients. Since VEGF synthesis is modulated not only by hypoxia but also by steroid hormones, we investigated the relationship between hypoxic and estrogenic/antiestrogenic stimuli in two human breast cancer cell lines expressing both ER6α and ERβ (MCF7) or only ERβ (MDA-MB231). In both cell lines, the VEGF level was significantly influenced by hypoxic conditions and in antiestrogen-responsive MCF7 cells, this effect was not counteracted by tamoxifen or ICI 182,780, thus providing an experimental explanation for the resistance to endocrine treatment observed in patients with ER-positive tumors. In MDA-MB231 cells, estradiol significantly reduced the VEGF level, suggesting that through the ERβ isoform it may function as a negative modulator of VEGF synthesis under hypoxia, and providing evidence for a complex interplay of the estrogen-dependent and hypoxia-dependent pathways.     

Immunocytochemical location of the centrosphere of human cancer cells using natural rabbit antibodies]

Sera of 40 normal nonimmunized rabbits were eprouved by immunoperoxidase on cultural human cells. Four sera contain centrosphere-reactive antibodies and for the strongest serum the centrospheres were still stained with the 1/600 dilution. This last serum visualized the centrospheres within the height human cell lines eprouved, whatever the phase of the mitotic cycle. The staining was not inhibited after serum absorption by tubulin.     

Are intermediate filaments of vertebrate smooth muscle cells and tonofilaments of epithelial cells identical cell structures?

Summary In epithelial and smooth muscle cells of the urinary bladder of the frog, a class of filaments exists which is partly disintegrated by glycerol treatment and very resistant to potassium solutions of high ionic strength.We are indebted to Miss M. Schlatter for her technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (He 686/2).     

Impact of interactions between normal and transformed epithelial cells and the relevance to cancer

The majority of human cancers are initiated when a single cell in an epithelial sheet becomes transformed. Cell transformation arises from the activation of oncoproteins and/or inactivation of tumor suppressor proteins. Recent studies have independently revealed that interaction and communication between transformed cells and their normal neighbors have a significant impact on the fate of the transformed cell. Several reports have shown that various phenomena occur at the interface between normal and transformed epithelial cells following the initial transformation event. In epithelia of Drosophila melanogaster, transformed and normal cells compete for survival in a process termed cell competition. This review will summarize current research and discuss the impact of these studies on our understanding of how primary tumors emerge and develop within a normal epithelium.     

Asymmetric cell division of stem and progenitor cells during homeostasis and cancer

Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer.     

Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A breast cancer cells: consequences on calcium signalling,cell migration and proliferation

Store-operated Ca²⁺ entry is a pathway that is remodelled in a variety of cancers, and altered expression of the components of store-operated Ca²⁺ entry is a feature of breast cancer cells of the basal molecular subtype. Studies of store-operated Ca²⁺ entry in breast cancer cells have used non-specific pharmacological inhibitors, complete depletion of intracellular Ca²⁺ stores and have mostly focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies compared the effects of the selective store-operated Ca²⁺ entry inhibitors Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca²⁺ ([Ca²⁺]_CYT) changes induced by physiological stimuli in a different breast cancer basal cell line model, MDA-MB-468. The effects of these agents on proliferation as well as serum and epidermal growth factor (EGF) induced migration were also assessed. Activation with the purinergic receptor activator adenosine triphosphate, produced a sustained increase in [Ca²⁺]_CYT that was entirely dependent on store-operated Ca²⁺ entry. The protease activated receptor 2 activator, trypsin, and EGF also produced Ca²⁺ influx that was sensitive to both Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells was sensitive to both store-operated Ca²⁺ inhibitors. However, proliferation and EGF-activated migration was differentially affected by Synta66 and YM58483. These studies highlight the need to define the exact mechanisms of action of different store-operated calcium entry inhibitors and the impact of such differences in the control of tumour progression pathways.     

Immunohistochemical individualization of adenohypophyseal thyrotropic cells in the monkey Macaca irus, using a human anti-beta-TSH antibody

Using the indirect immunofluorescence technique and an antiserum against the specific beta subunit of human TSH, selective immunocytochemical staining was localized in a cell population of the pars distalis of the monkey Macaca irus. These thyrotropic cells, which were positive to aldehyde fuchsin, Alcian blue, and PAS, were localized on the one hand in the ventro-medial zone of the pars distalis, especially alongside the large vessels of this region, and on the other in the zona tuberalis, i. e. at the bottom of the pars tuberalis. Some cells, sparsely distributed, were seen in the posterior part of the lateral lobes of the pars distalis, in the vicinity of the pars intermedia. No thyrotropic cells were encountered in pars tuberalis. Pars intermedia and posterior lobe contained no cells immunoreactive to beta-hTSH. In females, the thyrotropic cells were more numerous and larger than in males. Generally the thyrotropic cells were round or oval in shape, sometimes they were polygonal.     

Assessment of superoxide-mediated release of vascular-inhibitory factor(s) from endothelial cells by using a two-bath system

Summary Release of a vascular-inhibitory factor from endothelial cells (EC), different from endothelium-derived relaxant factor (EDRF), was identified through use of a two-bath system. This two-bath system precluded the effects of oxygen-free radicals that appear when electrical field stimulation (EFS) is directly imposed on detector muscle.     

Assessment of superoxide-mediated release of vascular-inhibitory factor(s) from endothelial cells by using a two-bath system

Release of a vascular-inhibitory factor from endothelial cells (EC), different from endothelium-derived relaxant factor (EDRF), was identified through use of a two-bath system. This two-bath system precluded the effects of oxygen-free radicals that appear when electrical field stimulation (EFS) is directly imposed on detector muscle.