Three-dimensional multicellular cell culture for anti-melanoma drug screening: focus on tumor microenvironment

AbstractThe development of new treatments for malignant melanoma, which has the worst prognosis among skin neoplasms, remains a challenge. The tumor microenvironment aids tumor cells to grow and resist to chemotherapeutic treatment. One way to mimic and study the tumor microenvironment is by using three-dimensional (3D) co-culture models (spheroids). In this study, a melanoma heterospheroid model composed of cancer cells, fibroblasts, and macrophages was produced by liquid-overlay technique using the agarose gel. The size, growth, viability, morphology, cancer stem-like cells population and inflammatory profile of tumor heterospheroids and monospheroids were analyzed to evaluate the influence of stromal cells on these parameters. Furthermore, dacarbazine cytotoxicity was evaluated using spheroids and two-dimensional (2D) melanoma model. After finishing the experiments, it was observed the M2 macrophages induced an anti-inflammatory microenvironment in heterospheroids; fibroblasts cells support the formation of the extracellular matrix, and a higher percentage of melanoma CD271 was observed in this model. Additionally, melanoma spheroids responded differently to the dacarbazine than the 2D melanoma culture as a result of their cellular heterogeneity and 3D structure. The 3D model was shown to be a fast and reliable tool for drug screening, which can mimic the in vivo tumor microenvironment regarding interactions and complexity.Graphic abstract      

Some aspects of decomposition of leaf litter of the seagrass Halophila stipulacea from the gulf of Aqaba (Jordan)

Decomposition of the seagrass Halophila stipulacea (Forsk.) Aschers. followed in situ over 340 days showed that the plant lost 40.8% of its initial weight during the first 85 days and only 21.2% over the remaining 255 days of the incubation period. The observed overall rate of decay of 0.18% day^?1 indicates the high resistance of Halophila tissue to decomposition.An exponential model showing a regularly decreasing decay coefficient was fitted to the data of weight loss. The correlation between observed and calculated weight remaining was highly significant (r = 0.9881, P < 0.0001).The samples of decomposing leaf litter harboured 2.2 × 10¹¹ bacteria g^?1 dry wt. on average and consumed 0.25?1.07 mg O₂^?1 dry wt. h^?1. The early colonizing bacteria of the detritus were mostly non-sporogenous forms. The most prominent genera involved in decomposition were Actinomyces, Arthrobacter, Bacillus and Pseudomonas, all of which are capable of degrading structural carbohydrates.