Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia

Kasashima, Hiroaki; Yashiro, Masakazu; Kinoshita, Haruhito; Fukuoka, Tatsunari; Morisaki, Tamami; Masuda, Go; Sakurai, Katsunobu; Kubo, Naoshi; Ohira, Masaichi; Hirakawa, Kosei

doi:10.1007/s10120-015-0510-3

Cited by 64 publications

(62 citation statements)

References 50 publications

(69 reference statements)

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“…Since the LOX family have an important role in stroma [18], our two-dimensional in vitro experiments have limitations and these results should be interpreted carefully. We have previously analyzed the significance of LOX and LOXL2 expressions using the same samples and reported that they were both independent prognostic factors [17,18]. These findings suggest that the expression of LOX family members might be closely associated with the progression of gastric cancer, and thus may be a promising therapeutic target for gastric cancer treatments.…”

Section: Discussionmentioning

confidence: 98%

“…As LOX was an independent prognostic factor among same samples [17], the poor prognosis of LOXL1 positive patients might be interfered by that of LOX positive patients. Since the LOX family have an important role in stroma [18], our two-dimensional in vitro experiments have limitations and these results should be interpreted carefully.…”

Section: Discussionmentioning

confidence: 99%

“…The immunohistochemical determination of LOXL1, LOXL3, and LOXL4 was performed as previously reported using anti-LOXL1 (H-165: sc-66949, Santa Cruz, Dallas, TX, USA), anti-LOXL3 (A-2: sc-365286, Santa Cruz, Dallas, TX, USA), and anti-LOXL4 antibodies (bs-5790R, Bioss Inc., Woburn, MA, USA) [17,[21][22][23].…”

Section: Immunohistochemical Determination Of Loxl1 Loxl3 and Loxl4mentioning

confidence: 99%

“…It has been reported that transforming growth factor β (TGFβ) plays an important role in various aspects of the metastatic spread of cancer cells, such as migration, invasion, and epithelial-mesenchymal transition, via autocrine or paracrine manner [12][13][14][15][16]. We previously reported that LOX and LOXL2 expressions are associated with gastric cancer progression [17,18]. Here, we examined the significance of other LOX family members including LOXL1, LOXL3, and LOXL4 in gastric cancer, and analyzed the effect of TGFβ on the expression of the LOX family.…”

Section: Introductionmentioning

confidence: 99%

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Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Kasashima¹,

Yashiro²,

Okuno³

et al. 2018

Digestion

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Background/Aims: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. Methods: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members – LOXL1, LOXL3, and LOXL4 – were investigated by immunohistochemical studies. The effect of the transforming growth factor β1 (TGFβ1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. Results: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFβ decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. Conclusion: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemical Determination Of Loxl1 Loxl3 and Loxl4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Kasashima¹,

Yashiro²,

Okuno³

et al. 2018

Digestion

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“…44,45 Stromal-derived LOX could create a milieu that is suitable for metastastic cancer cells. 34,46 Recently, LOX has been considered as one target to control the metastasis of prostate cancer.…”

mentioning

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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Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

et al. 2023

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The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases. These insights have considerably stimulated drug discovery efforts towards lysyl oxidases as targets over the last decade. This review article summarises the biochemical and structural properties of theses enzymes. Their involvement in tumour progression and metastasis is highlighted from a biochemical point of view, taking into consideration both the extracellular and intracellular action of lysyl oxidases. More recently reported inhibitor compounds are discussed with an emphasis on their discovery, structure‐activity relationships and the results of their biological characterisation. Molecular probes developed for imaging of lysyl oxidase activity are reviewed from the perspective of their detection principles, performance and biomedical applications.

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Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia

Cited by 64 publications

References 50 publications

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

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

Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

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