Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer

The extracellular matrix (ECM) is a complex network of secreted proteins which provides support for tissues and organs. Additionally, the ECM controls a plethora of cell functions, including cell polarity, migration, proliferation, and oncogenic transformation. One of the hallmarks of cancer is altered cell metabolism, which is currently being exploited to develop anti-cancer therapies. Several pieces of evidence indicate that the tumor microenvironment and the ECM impinge on tumor cell metabolism. Therefore, it is essential to understand the contribution of the complex 3D microenvironment in controlling metabolic plasticity and responsiveness to therapies targeting cell metabolism. In this mini-review, we will describe how the tumor microenvironment and cancer-associated fibroblasts dictate cancer cell metabolism, resulting in increased tumor progression. Moreover, we will define the cross-talk between nutrient signaling and the trafficking of the ECM receptors of the integrin family. Finally, we will present recent data highlighting the contribution of nutrient scavenging from the microenvironment to support cancer cells growth under nutrient starvation conditions

The reproduction biology of Abudefduf sexfasciatus in the Persian Gulf (Larak Island)

The reproduction biology of A. sexfasciatus, one of the main and important ornamental fishes in the Persian Gulf were studied during 1997-98. For sampling, Larak island sited on south-eastern of Bandar-Abbas was chosen. The main fishing gear was hook for collecting samples. During this investigation, weight, length (FL & T.L), GSI, HSI, Kf, sex ratio, LM50 and sexual overlap zone were measured or calculated. Also, the histological studies were done on gonads. The results showed that this species is a protogenous hermaphrodite. A. sexfasciatus has an allometric growth and the results of GSI, HSI and Kf indicated that the spawning season occured in spring as a total spawner species. The sex ratio was found M:F=1.00:1.24 without any significant difference. The overlap zone was recongnized 30mm (with a range of 125-155mm). The LM50 was calculated 130-140mm for females and 160-170mm for males. The size at first maturity for females and males were determined 105 and 120mm, respectively

Exploring wind direction and SO2 concentration by circular-linear density estimation

The study of environmental problems usually requires the description of variables with different nature and the assessment of relations between them. In this work, an algorithm for flexible estimation of the joint density for a circular-linear variable is proposed. The method is applied for exploring the relation between wind direction and SO2 concentration in a monitoring station close to a power plant located in Galicia (NW-Spain), in order to compare the effectiveness of precautionary measures for pollutants reduction in two different years.Comment: 17 pages, 7 figures, 2 table

Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in Aqueous Media

Cylindrical block copolymer micelles have shown considerable promise in various fields of biomedical research. However, unlike spherical micelles and vesicles, control over their dimensions in biologically relevant solvents has posed a key challenge that potentially limits in depth studies and their optimization for applications. Here, we report the preparation of cylindrical micelles of length in the wide range of 70 nm to 1.10 μm in aqueous media with narrow length distributions (length polydispersities <1.10). In our approach, an amphiphilic linear-brush block copolymer, with high potential for functionalization, was synthesized based on poly­(ferrocenyldimethylsilane)-<i>b</i>-poly­(allyl glycidyl ether) (PFS-<i>b</i>-PAGE) decorated with triethylene glycol (TEG), abbreviated as PFS-<i>b</i>-(PEO-<i>g</i>-TEG). PFS-<i>b</i>-(PEO-<i>g</i>-TEG) cylindrical micelles of controlled length with low polydispersities were prepared in <i>N</i>,<i>N</i>-dimethylformamide using small seed initiators via living crystallization-driven self-assembly. Successful dispersion of these micelles into aqueous media was achieved by dialysis against deionized water. Furthermore, B–A–B amphiphilic triblock comicelles with PFS-<i>b</i>-poly­(2-vinylpyridine) (P2VP) as hydrophobic “B” blocks and hydrophilic PFS-<i>b</i>-(PEO-<i>g</i>-TEG) “A” segments were prepared and their hierarchical self-assembly in aqueous media studied. It was found that superstructures formed are dependent on the length of the hydrophobic blocks. Quaternization of P2VP was shown to cause the disassembly of the superstructures, resulting in the first examples of water-soluble cylindrical multiblock comicelles. We also demonstrate the ability of the triblock comicelles with quaternized terminal segments to complex DNA and, thus, to potentially function as gene vectors

The extracellular matrix promotes breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism

Breast cancer tumours are embedded in a collagen I rich extracellular matrix (ECM) network where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for breast cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the upregulation of the intracellular levels of several amino acids, including tyrosine and phenylalanine. Finally, we showed that cells on ECM had elevated tyrosine catabolism, leading to elevated fumarate levels, potentially feeding into the tricarboxylic acid cycle. Interestingly, this pathway was required for ECM-dependent cell growth under amino acid starvation, as the knockdown of HPDL, the third enzyme of the pathway, opposed cell growth on ECM without affecting cell proliferation on plastic. Collectively, our results highlight that the ECM surrounding breast cancer tumours represents an alternative source of nutrients to support cancer cell growth, by regulating phenylalanine and tyrosine metabolism

The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism

Breast tumours are embedded in a collagen I-rich extracellular matrix (ECM) network, where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required macropinocytosis-dependent ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the up-regulation of the intracellular levels of several amino acids, most notably tyrosine and phenylalanine. This resulted in elevated tyrosine catabolism on ECM under starvation, leading to increased fumarate levels, potentially feeding into the tricarboxylic acid (TCA) cycle. Interestingly, this pathway was required for ECM-dependent cell growth and invasive cell migration under amino acid starvation, as the knockdown of p-hydroxyphenylpyruvate hydroxylase-like protein (HPDL), the third enzyme of the pathway, opposed cell growth and motility on ECM in both 2D and 3D systems, without affecting cell proliferation on plastic. Finally, high HPDL expression correlated with poor prognosis in breast cancer patients. Collectively, our results highlight that the ECM in the tumour microenvironment (TME) represents an alternative source of nutrients to support cancer cell growth by regulating phenylalanine and tyrosine metabolism

Knowledge Sharing Idiosyncrasies of University Students in Ghana

Part 6: Decision Making and Knowledge ManagementInternational audienceThis study explored the factors affecting knowledge sharing behaviour of students in a higher institution of learning. Using a model derived from the Social Cognitive Theory and the Theory of Reason Action, six hypotheses were tested from a cross-sectional data collected from 371 undergraduate students on a 4-year degree programme in the University of Ghana. Five out of the six hypotheses were supported. The results showed that the knowledge sharing behaviour (KSB) of the students was significantly related to five of the human and environmental factors (F=639.9, df=5, 290, p<0.05) with a co-efficient of variation of R2=0.917 (91.7%). The knowledge sharing behavior of the students was, however, not significantly dependent on their personal characteristics. The study makes a case for increased attention in understanding the human and environmental factors of knowledge sharing since knowledge sharing is largely a people activity shaped by culture