LOX Expression and Functional Analysis in Astrocytomas and Impact of IDH1 Mutation

Silva, Roseli da; Uno, Miyuki; Marie, Suely Kazue Nagahashi; Oba-Shinjo, Sueli Mieko

doi:10.1371/journal.pone.0119781

Cited by 45 publications

(38 citation statements)

References 64 publications

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“…MMPs break down fibrous ECM structures, like collagen, to create reorganization within the tumor, and they lead to changes in physical properties. Traditionally, increases in MMP expression and LOX expression are associated with high-grade tumors (24,25). However, in the context of optic nerve glioma, we saw a decrease in MMP-2 and no change in LOX, which suggests less breakdown of collagen fibers (a greater degree of collagen cross-linking).…”

Section: Ecm-modifying Enzyme Expression Is Altered In Glioma-bearingmentioning

confidence: 60%

Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma

Walter

Crawford

Lai

et al. 2017

Biophysical Journal

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Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue. We found that the average elastic moduli of non-neoplastic and tumor-bearing optic nerves were ∼3 and ∼6 kPa, respectively. Based on previous studies implicating changes in extracellular matrix remodeling in other, related optic nerve pathological states, we found decreased expression of one major metalloproteinase protein (MMP-2) and unchanged expression of lysyl oxidase and a second metalloproteinase, MMP-9, in murine optic gliomas relative to normal non-neoplastic optic nerve. Collectively, these observations suggest a productive interplay between physical properties of mouse optic nerve gliomas and the extracellular matrix.

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Section: Ecm-modifying Enzyme Expression Is Altered In Glioma-bearingmentioning

confidence: 60%

Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma

Walter

Crawford

Lai

et al. 2017

Biophysical Journal

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“…High expression of LOX is related to worse outcome in some cancer, such as astrocytomas, non-small lung cancer and GC. [37][38][39] Notably, the protein LOX has also been shown to have antitumor activity in several cancer types, including GC, lung cancer and nasopharyngeal carcinoma. [40][41][42] In this study, we also found that the expression of LOX was significantly increased in tumor tissues compared to peritumoral tissues.…”

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confidence: 99%

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

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Purpose Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ. Patients and methods A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated. Results This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival ( P <0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup ( P <0.001). Conclusion Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs.

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“…For example, Agra et al (2013) showed that EWS/FLI1 downregulates LOX expression and that, remarkably, LOX propeptide exhibits tumor suppressor activities in Ewing tumor cells. Da Silva et al (2015) confirmed that LOX plays an important role in migration and angiogenesis in diffusively infiltrative astrocytomas, and LOX expression is influenced by IDH1 mutational status. Furthermore, cancer progression is closely related to its microenvironment, such as the extracellular matrix around the tumor (Allen and Louise Jones, 2011).…”

Section: Discussionmentioning

confidence: 76%

“…LOX is an extracellular copper-containing enzyme which catalyzes the crosslinking of collagen and elastin, and plays a critical role in extracellular matrix organization (da Silva et al, 2015). Increasing evidence suggests that LOX is involved in tumor progression and metastasis, while its role in tumorigenesis is still contradictory (Boufraqech et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

miR-29b regulates cell proliferation and invasion in human ovarian clear cell carcinoma by targeting Lysyl oxidase (LOX)

Wang

et al. 2016

ARCH BIOL SCI BELGRA

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Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX) is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs (miRNAs) were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNA in ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation by changing the level of miR-29b expression could provide a novel potential approach for treating human ovarian clear cell carcinoma.

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LOX Expression and Functional Analysis in Astrocytomas and Impact of IDH1 Mutation

Cited by 45 publications

References 64 publications

Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma

Increased Tissue Stiffness in Tumors from Mice with Neurofibromatosis-1 Optic Glioma

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

miR-29b regulates cell proliferation and invasion in human ovarian clear cell carcinoma by targeting Lysyl oxidase (LOX)

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