concanavalin-a and Retinoblastoma

Retinoblastoma (RB), an intraocular tumor of childhood, contains small subpopulation(s) of stem-like cells expressing the ABCG2 drug transporter that can efflux standard chemotherapies. Since chemo-resistant stem-like cells appear to be a driving force in tumor progression and metastasis for a variety of cancers, innovative treatment strategies are necessary to eradicate these rare cell populations. Terminal differentiation, as a means to deplete the pool of stem-like cells in RB, is an intriguing approach to cancer therapeutics. However, the full extent of RB differentiation remains unknown. Differentiation of RB cells has been examined in response to a variety of different agents, including retinoic acid/sodium butyrate, Pigment Epithelial-Derived Factor, as well as Succinylated Concanavalin A. RB cells exhibit morphologic and phenotypic responses to these differentiating agents, although the permanence of these effects is questionable due to reversibility. Further study of differentiation programs may lead to new approaches in the design of strategies to combat the initiation and progression of RB in vivo.

Topics: Antineoplastic Agents; Butyrates; Cell Differentiation; Concanavalin A; Eye Proteins; Humans; Neoplastic Stem Cells; Nerve Growth Factors; Retinoblastoma; Serpins; Tretinoin; Tumor Cells, Cultured

Porphyrins are photosensitizers usable in photodynamic therapy. Although these molecules are clinically effective, their low water solubility and their lack of specificity are major drawbacks to their development. Our study was aimed at analysing the interfacial behaviour of glycoconjugated tetraphenylporphyrins newly synthesized at the Curie Institute, and their interaction with model membranes bearing a specific lectin mimicking a mannose membrane receptor in retinoblastoma.. The interfacial behaviour of the porphyrins was analysed by surface pressure measurements, and their specific interaction with the lectin, by dynamic light scattering (liposomes) and the quartz crystal microbalance technique (supported bilayers).. All porphyrin derivatives were able to organize at the air/liquid interface. The dendrimeric compounds formed more stable monolayers than the others, and generally showed good mixing properties with the phospholipid used for liposome preparation. In the presence of concanavalin A, the porphyrin bearing-liposomes behaved differently depending on the nature (mannosylated or not) of the porphyrins.. The interfacial behaviour of the tetraphenylporphyrins is directly related to the orientation of the tetrapyrrolic macrocycle controlled by the grafted groups. Incorporated into a liposome bilayer, glycodendrimeric porphyrins expose their sugar moieties at the vesicle surface. The spacer length plays a crucial role by increasing sugars freedom and enhancing glycosylated liposomes interaction with the lectin.. Compared to the other studied compounds, the glycodendrimeric porphyrins seem very promising compounds and are now evaluated on cell cultures.

Topics: Biomimetics; Cell Line, Tumor; Cell Membrane; Concanavalin A; Dendrimers; Glycoconjugates; Humans; Lectins; Membranes, Artificial; Phospholipids; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retinal Neoplasms; Retinoblastoma; Surface Properties

Photodynamic therapy is a potentially efficient treatment for various solid tumours, among which retinoblastoma. Its efficacy depends on the preferential accumulation of photosensitizers in the malignant tissues and their accessibility to light. The specificity of drugs for retinoblastoma cells can be improved by targeting a mannose receptor overexpressed at their surface. With the aim of assessing the recognition of newly synthesized glycodendrimeric porphyrins by such receptors, we have built and characterized an original synthetic biomimetic membrane having similar lipidic composition to that of the retinal cell membranes and bearing Concanavalin A, as a model of the mannose receptor. The interaction of the porphyrin derivatives with liposomes and supported planar bilayers has been studied by dynamic light scattering and quartz crystal microbalance with dissipation monitoring (QCM-D). Only mannosylated porphyrins interacted significantly with the membrane model. The methodology used proved to be efficient for the selection of potentially active compounds.

Topics: Biomimetics; Cell Membrane; Concanavalin A; Humans; Lectins; Lipid Bilayers; Liposomes; Mannose; Porphyrins; Quartz Crystal Microbalance Techniques; Retinoblastoma; Tumor Cells, Cultured

The growth and differentiation potential of Y79 human retinoblastoma cells was assessed in vitro following treatment with the differentiating agent succinylated concanavalin A (SCA). Since SCA treatment induced Y79 cells to display differentiated morphologies in vitro, we sought to determine potential differentiated phenotypes with the use of retinal cell markers. Seventy-two h after SCA treatment, Y79 cells exhibited a decrease in the glial cell marker GFAP and a dramatic and reversible increase in the photoreceptor marker IRBP, while maintaining neuron-specific enolase and PGP 9.5 positivity. These results were indicative of a predominantly neuronal, photoreceptor cell population in response to SCA treatment. In addition, Y79 cell growth inhibition was observed in response to SCA, which could be reversed within 24 h of treatment with the blocking sugar alpha-methyl-D-mannoside. These changes were accompanied by a significant modulation of the N-MYC oncoprotein, as detected by Western blot analysis and immunocytochemistry. Thus, in this system, the status of N-MYC seems to be closely linked to changes in the growth and differentiated state of SCA-treated Y79 retinoblastoma cells.

Topics: Cell Differentiation; Cell Division; Concanavalin A; Eye Proteins; Humans; Mitotic Index; Neuroglia; Neurons; Phenotype; Proto-Oncogene Proteins c-myc; Retinoblastoma; Retinol-Binding Proteins; Tumor Cells, Cultured