Collagen VI at a glance Cescon, Matilde; Gattazzo, Francesca; Chen, Peiwen ...
Journal of cell science,
10/2015, Volume:
128, Issue:
19
Journal Article
Peer reviewed
Open access
Collagen VI represents a remarkable extracellular matrix molecule, and in the past few years, studies of this molecule have revealed its involvement in a wide range of tissues and pathological ...conditions. In addition to its complex multi-step pathway of biosynthesis and assembly that leads to the formation of a characteristic and distinctive network of beaded microfilaments in the extracellular matrix, collagen VI exerts several key roles in different tissues. These range from unique biomechanical roles to cytoprotective functions in different cells, including myofibers, chondrocytes, neurons, fibroblasts and cardiomyocytes. Indeed, collagen VI has been shown to exert a surprisingly broad range of cytoprotective effects, which include counteracting apoptosis and oxidative damage, favoring tumor growth and progression, regulating autophagy and cell differentiation, and even contributing to the maintenance of stemness. In this Cell Science at a Glance article and the accompanying poster, we present the current knowledge of collagen VI, and in particular, discuss its relevance in stemness and in preserving the mechanical properties of tissues, as well as its links with human disorders.
Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) ...are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single-cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM-targeted therapeutics for GBM patients.
Autophagy is a highly conserved homeostatic pathway that plays an important role in tumor development and progression by acting on cancer cells in a cell-autonomous mechanism. However, the solid ...tumor is not an island, but rather an ensemble performance that includes nonmalignant stromal cells, such as macrophages. A growing body of evidence indicates that autophagy is a key component of the innate immune response. In this review, we discuss the role of autophagy in the control of macrophage production at different stages (including hematopoietic stem cell maintenance, monocyte/macrophage migration, and monocyte differentiation into macrophages) and polarization and discuss how modulating autophagy in tumor-associated macrophages (TAMs) may represent a promising strategy for limiting cancer growth and progression.
Highlights • This review extensively discusses the key role of collagen VI in cancer. • Collagen VI promotes tumor progression by affecting both tumor cell and stromal cell. • Collagen VI is a potent ...promoter of chemotherapy resistance. • Collagen VI is a potential biomarker for cancer diagnosis. • The article highlights a feasible anticancer strategy by suppressing collagen VI.
Macrophages are prominent immune cells in the tumor microenvironment that exert potent effects on cancer metastasis. However, the signals and receivers for the tumor–macrophage communication remain ...enigmatic. Here, we show that G protein-coupled receptor 132 (Gpr132) functions as a key macrophage sensor of the rising lactate in the acidic tumor milieu to mediate the reciprocal interaction between cancer cells and macrophages during breast cancer metastasis. Lactate activates macrophage Gpr132 to promote the alternatively activated macrophage (M2)-like phenotype, which, in turn, facilitates cancer cell adhesion, migration, and invasion. Consequently, Gpr132 deletion reduces M2 macrophages and impedes breast cancer lung metastasis in mice. Clinically, Gpr132 expression positively correlates with M2 macrophages, metastasis, and poor prognosis in patients with breast cancer. These findings uncover the lactate-Gpr132 axis as a driver of breast cancer metastasis by stimulating tumor–macrophage interplay, and reveal potential new therapeutic targets for breast cancer treatment.
Heterotypic interactions across diverse cell types can enable tumor progression and hold the potential to expand therapeutic interventions. Here, combined profiling and functional studies of glioma ...cells in glioblastoma multiforme (GBM) models establish that PTEN deficiency activates YAP1, which directly upregulates lysyl oxidase (LOX) expression. Mechanistically, secreted LOX functions as a potent macrophage chemoattractant via activation of the β1 integrin-PYK2 pathway in macrophages. These infiltrating macrophages secrete SPP1, which sustains glioma cell survival and stimulates angiogenesis. In PTEN-null GBM models, LOX inhibition markedly suppresses macrophage infiltration and tumor progression. Correspondingly, YAP1-LOX and β1 integrin-SPP1 signaling correlates positively with higher macrophage density and lower overall survival in GBM patients. This symbiotic glioma-macrophage interplay provides therapeutic targets specifically for PTEN-deficient GBM.
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•PTEN deficiency in GBM drives macrophage infiltration via upregulation of LOX•LOX is directly regulated by YAP1 in PTEN-deficient GBM•LOX recruits macrophages into GBM via the β1 integrin-PYK2 pathway•LOX inhibition impairs PTEN-deficient GBM progression by decreasing TAM-derived SPP1
Chen et al. find that PTEN deficiency in glioblastoma (GBM) increases macrophage infiltration via a YAP1-LOX-β1 integrin-PYK2 axis, the infiltrated macrophages in turn secrete SPP1 to support GBM survival. In PTEN-null GBM xenograft mouse models, inhibition of LOX reduces macrophage infiltration and tumor growth.
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•Three generations of pyrite are identified in the Baiyun gold deposit.•Oxidation of fluids caused the negative δ34S values of hydrothermal pyrite.•In situ analyses reveal that ...visible gold precipitated from metal-rich magmatic fluids.
Trace elements distribution in minerals and formation mechanism of visible gold are poorly understood in intrusion-related gold systems. Here, we choose the Baiyun gold deposit, which is hosted within the Paleoproterozoic metamorphic rocks in the Liaodong Peninsula, NE North China Craton (NCC), as a case study, to address these issues. The ore deposit geology characteristics and paragenesis are described in details; In situ geochemical and sulfur isotopic compositions of pyrite and bulk Pb isotopic ratios of pyrite were presented to define the genesis of pyrite that is closely associated with gold mineralization. Three generations of pyrite were recognized based on petrographic studies: metamorphic pyrite (Py0), hydrothermal pyrite (Py1) coexisting with milky quartz, and hydrothermal pyrite (Py2) coexisting with smoky quartz. In situ laser ablation-inductively coupled plasma-mass spectrometer (LA-ICP-MS) spot analysis suggests that both Py0 and Py1 contain low contents of invisible gold (mean 0.19 ppm and 0.17 ppm, respectively). However, Py1 is low in most other trace element contents and contains Au-Ag-Cu-Pb-Bi micro-inclusions. In contrast, Py2 contains both invisible gold (mean 0.50 ppm) and Au-Ag-Cu-Pb-Bi micro-inclusions. Furthermore, LA-ICP-MS mapping reveals the distributions of Ag, Cu, Pb, Bi and Te closely mimic that of Au, indicating an episode of ore-forming fluid rich in Au, Ag, Cu, Pb, Bi and Te. In situ sulfur isotope analysis of pyrite shows that Py0 has significantly positive δ34S values (+11.74–17.33‰), suggesting that sulfur was derived from sedimentary sources. Py1 and Py2 have negative δ34S values (–8.53––6.19‰, –10.44––6.86‰, respectively), indicating that sulfur was derived from oxidized magmatic fluids. The magmatic fluids are concluded to be released from the early Cretaceous microdiorite magmas, providing most of the sulfur and ore-forming metals. Proofs include the close spatial association of the ore bodies and the dykes, as well the uniform Pb isotopic ratios of Py1 and the early Cretaceous microdiorite. Lines of geological, mineralogical, geochemical and isotopic evidence consistently suggest that the gold mineralization in the Baiyun deposit is intrusion-related, and was resulted from the ~126 Ma magmatic-hydrothermal activities in the region. Visible gold precipitating in pyrite and fractures was from metal-rich magmatic fluids rather than being remobilized from the metamorphic pyrite.
As an ideal biomarker candidate, circulating tumor DNA (ctDNA) plays a vital role in noninvasive diagnosis of cancer. However, most traditional approaches for quantifying ctDNA are cumbersome and ...expensive. In the present work, a novel electrochemical biosensor based on nest hybridization chain reaction was proposed for the sensitive and specific detection of PIK3CA E545K ctDNA with a simple process. The nest hybridization chain reaction was initiated by the hybridization of two dumbbell-shaped DNA units which were assembled by two classes of well-designed DNA probes respectively, leading to the formation of a complex DNA structure. In the presence of target ctDNA, the amplified hybridization chain reaction products were captured by target ctDNA, resulting in a significant increase of electrochemical signal. Under the optimal conditions, the developed biosensor exhibited good analytical performance for the detection of target ctDNA with the linear range from 5 pM to 0.5 nM and the detection limit of 3 pM. Furthermore, this assay was successfully applied to the detection of ctDNA in spiked-in samples, pleural effusion and serum samples of malignant tumor patients. This simple and cost-effective sensing system holds great potentials for ctDNA detection and cancer diagnosis.
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•A novel electrochemical assay for detection of circulating tumor DNA is proposed.•The assay takes advantages of nest hybridization chain reaction for signal amplification.•The biosensor exhibits high sensitivity and specificity for ctDNA detection.•This biosensor has been applied in the detection of ctDNA in clinical samples and holds great potential in cancer diagnosis.
•Spatiotemporal differentiation characteristics of NPP in Shandong were presented.•NPP was predicted to experience a short-term decline in the near future.•The quantitative impact of NPP showed a ...pattern of “three zones and two lines”.
Exploring the spatiotemporal changes of vegetation net primary productivity (NPP) and its driving mechanism is crucial for green and low-carbon development. Based on the MOD17A3HGF data, this study introduced the gravity center model, wavelet analysis, coefficient of variation, Hurst index, correlation analysis, and Thornthwaite Memorial model to explore the spatiotemporal patterns of NPP and its driving factors in Shandong Province from 2000 to 2019. The following results were attained. (1) Between 2000 and 2019, Shandong’s yearly average NPP showed an upward trend. The first main cycle of the NPP’s interannual cycle lasted 14 years. NPP was predicted to experience a short-term decline in the near future. (2) In Shandong, the NPP displayed a geographical pattern with high values in the east and low values in the west, high values in the south and low values in the north, and progressively declining values from the coast to the interior. The growth rate and increment of NPP in 2000–2019 were the largest in the northeast direction in the Southwest Plain, while those in the Jiaodong Hills, the Central and Southern Mountains, and the Northwest Plain were the largest in the northwest direction. Hurst index analysis showed that NPP would show weak anti-continuity changes in the Central and Southern Mountains and the Jiaodong Hills in the future. (3) Shandong’s NPP exhibited a “three zones and two lines” pattern of the effect of climate change and human activities. This research offers a scientific theoretical foundation for environmental protection and carbon management.
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•The geochronological framework of the Wulong orefield has been reconstructed.•Zircon U-Pb geochronology delineates the two main magmatic events in the Wulong orefield.•Molybdenite ...Re-Os and monazite U-Th-Pb geochronology record the Wulong gold mineralization occurred at 127 Ma.•The Wulong gold mineralization is contemporaneous with the Early Cretaceous magmatism, related to lithospheric thinning under the northeastern North China Craton.
The Wulong deposit is a large tonnage deposit (>80 t of Au), characterized by quartz vein style of gold mineralization in the Liaodong Peninsula, China. The auriferous quartz veins are mainly hosted by Late Jurassic gneissic two-mica granite (165–157 Ma) and Early Cretaceous granodiorite (129 Ma) and are structurally controlled by NNE- and NW-trending faults. Previous attempts to date the gold mineralization yielded ambiguous results (135–112 Ma). Here we report the first in-situ and direct age constraint for gold mineralization at Wulong. Five molybdenite samples from Mo-bearing quartz ± pyrite veins yielded an isochron age of 127.6 ± 2.3 Ma. In-situ SIMS U-Th-Pb dating of hydrothermal monazite that coexists with gold-bearing pyrite and quartz yielded a 208Pb-232Th age of 126.7 ± 3.2 Ma. These robust ages, together with new age data of the Wulong host intrusion and post-ore dike, allow for a better interpretation of the ore genesis of the Wulong deposit relative to a well constrained sequence of regional geological events. Zircon U-Pb dating of the Wulong host intrusion (gneissic two-mica granite), representing the oldest magmatic event at Wulong, gave a weighted mean age of 159.3 ± 1.4 Ma that is interpreted to be the magma emplacement age. Subsequent magmatic events are recorded by the Early Cretaceous dikes with zircon U-Pb ages between 127 and 113 Ma. A post-ore diorite porphyry dike that crosscuts the Early Cretaceous dikes has a U-Pb zircon age of 121.5 ± 1.5 Ma. All the lines of geochronology evidence suggest a distinct genetic link between the gold mineralization and the Early Cretaceous magmatism in the Wulong orefield. This episode of magmatism and mineralization corresponds to the lithospheric thinning within the northeastern North China Craton, which is triggered by the subduction of the Paleo-Pacific plate.
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