bims-prodis 2018-10-21 papers

Issue of 2018–10–21
two papers selected by
Nancy Gough, Bioserendipity

Semin Cancer Biol. 2018 Oct 11. pii: S1044-579X(18)30049-X. [Epub ahead of print]

Tumour Microenvironment and Metabolic Plasticity in Cancer and Cancer Stem Cells: Perspectives on Metabolic and Immune Regulatory Signatures in Chemoresistant Ovarian Cancer Stem Cells.

Nuzhat Ahmed, Ruth Escalona, Dilys Leung, Emily Chan, George Kannourakis.

Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.

Keywords: ascites; cancer stem cells; cancer-associated fibroblasts; chemoresistance; endothelial cells; immune cells; ovarian carcinoma; tumour cells

DOI: https://doi.org/10.1016/j.semcancer.2018.10.002

Am J Ophthalmol. 2018 Oct 11. pii: S0002-9394(18)30590-7. [Epub ahead of print]

Cytokine levels in the aqueous humor are associated with corneal thickness in eyes with bullous keratopathy.

Natsume Suzuki, Takefumi Yamaguchi, Shinsuke Shibata, Toshihiro Nagai, Hisashi Noma, Kazuo Tsubota, Jun Shimazaki.

PURPOSE: To investigate the association between the severity of bullous keratopathy and proinflammatory cytokine levels in the aqueous humor (AqH).
DESIGN: Cross sectional study.
METHODS: This study included a total of 95 eyes: 62 with bullous keratopathy and 33 that underwent cataract surgery. Central corneal thickness (CCT) and central corneal volume within 4mm and 6mm (CCV4mm and CCV6mm, respectively) were determined using anterior segment optical coherence tomography. A total of 95 AqH samples were collected at the beginning of surgery. The levels of cytokines (interleukin[IL]-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon [IFN]-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin and P-selectin) in the AqH were measured using multiplex beads immunoassay. We evaluated the correlation among AqH cytokine levels, CCT, CCV4mm and CCV6mm in eyes with bullous keratopathy.
RESULTS: The levels of protein, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, MCP-1, IFN-γ, E-selectin, P-selectin, and sICAM-1 were significantly higher in eyes with bullous keratopathy compared with those of the normal controls (all, P < 0.0025). CCT was significantly correlated with the levels of IL-13 (r = 0.551, P = 0.0009), and sICAM-1 (r = 0.448, P = 0.0005). CCV4mm was significantly correlated with the levels of IL-13 (r = 0.514, P = 0.0022), and sICAM-1 (r = 0.404, P = 0.0019). CCV6mm was significantly correlated with the level of sICAM-1 (r = 0.459, P = 0.0003).
CONCLUSION: The severity of corneal edema in eyes with bullous keratopathy was associated with the levels of specific cytokines in the AqH.

Keywords: Aqueous humor; Bullous keratopathy; Corneal thickness; Cytokine

DOI: https://doi.org/10.1016/j.ajo.2018.10.008