SPOCK1 with unexpected function. The start of a new career

Váncza, Lóránd; Tátrai, Péter; Reszegi, Andrea; Baghy, Kornélia; Kovalszky, Ilona

doi:10.1152/ajpcell.00033.2022

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…In tumor tissues, the tumor cells mainly exhibited moderate or strong diffuse granular cytoplasmic SPOCK1 staining. The granular staining seen for SPOCK1 in our study has been previously documented in liver tumor cells [ 15 , 22 ], where the proteoglycan colocalized with mitochondrial markers. Given the similar pattern observed in ovarian carcinomas, it is possible that SPOCK1 resides in the mitochondria.…”

Section: Discussionsupporting

confidence: 84%

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SPOCK1 Overexpression Suggests Poor Prognosis of Ovarian Cancer

Váncza

Horváth

Seungyeon

et al. 2023

Cancers

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Purpose: Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been found in a variety of malignant tumors and is associated with a poor prognosis. We aimed to explore the role of SPOCK1 in ovarian cancer. Methods: Ovarian cancer cell lines SKOV3 and SW626 were transfected with SPOCK1 overexpressing or empty vector using electroporation. Cells were studied by immunostaining and an automated Western blotting system. BrdU uptake and wound healing assays assessed cell proliferation and migration. SPOCK1 expression in human ovarian cancer tissues and in blood samples were studied by immunostaining and ELISA. Survival of patients with tumors exhibiting low and high SPOCK1 expression was analyzed using online tools. Results: Both transfected cell lines synthesized different SPOCK1 variants; SKOV3 cells also secreted the proteoglycan. SPOCK1 overexpression stimulated DNA synthesis and cell migration involving p21CIP1. Ovarian cancer patients had increased SPOCK1 serum levels compared to healthy controls. Tumor cells of tissues also displayed abundant SPOCK1. Moreover, SPOCK1 levels were higher in untreated ovarian cancer serum and tissue samples and lower in recipients of chemotherapy. According to in silico analyses, high SPOCK1 expression was correlated with shorter survival. Conclusion: Our findings suggest SPOCK1 may be a viable anti-tumor therapeutic target and could be used for monitoring ovarian cancer.

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Section: Discussionsupporting

confidence: 84%

“…SPOCK proteins possess GAG chains, allowing them to interact not only via their protein core, but also through their sugar chains. All three members of the Testican/SPOCK family have a similar 5-domain structure [ 22 ]. However, the literature provides little information regarding their structural properties or changes.…”

Section: Discussionmentioning

confidence: 99%

SPOCK1 Overexpression Suggests Poor Prognosis of Ovarian Cancer

Váncza

Horváth

Seungyeon

et al. 2023

Cancers

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“…Hence, it may have role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. In HepG2 cells overexpression of miR-193-5p inhibited cell growth and targeted SPOCK1 (139), a matricellular proteoglycan associated with hepatocellular carcinoma (140), while in liver RNA-seq data, levels of miR-193a-5p were positively correlated with the anti-oxidative glutathione peroxidase, GPX8 (138)(Figure 2).…”

Section: Increased Circulating Levels Of Mir-193a and Mir-192 Are Ass...mentioning

confidence: 99%

Circulating miRNAs associated with nonalcoholic fatty liver disease

Atic

Thiele

Munk

et al. 2023

American Journal of Physiology-Cell Physiology

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MicroRNAs (miRNAs) are secreted from cells as either protein bound or enclosed in extracellular vesicles. Circulating liver-derived miRNAs are modifiable by weight-loss or insulin-sensitizing treatments, indicating that they could be important biomarkers candidates for diagnosis, monitoring, and prognosis in NAFLD (non-alcoholic liver disease) and NASH (non-alcoholic steatohepatitis). Unfortunately, the non-invasive diagnosis of NASH and fibrosis remains a key challenge, which limits case finding. Current diagnostic guidelines therefore recommend liver biopsies, with risks of pain and bleeding for the patient and substantial healthcare costs. Here, we summarize mechanisms of RNA secretion, and review circulating RNAs associated with NAFLD and NASH for their biomarker potential. Few circulating miRNAs are consistently associated with NAFLD/NASH: miR-122, miR-21, miR-34a, miR-192, miR-193 and the miR-17-92 miRNA-cluster. The hepatocyte-enriched miRNA-122 is consistently increased in NAFLD and NASH but decrease in liver cirrhosis. Circulating miR-34a, part of an existing diagnostic algorithm for NAFLD, and miR-21 are consistently increased in NAFLD and NASH. MiR-192 appears to be prominently upregulated in NASH compared with NAFDL, whereas miR-193 was reported able to distinguish NASH from fibrosis. Various members of miRNA cluster miR-17-92 are reported associated with NAFLD and NASH, although with less consistency. Several other circulating miRNAs have been reported associated with fatty liver in few studies, indicating the existence of more circulating miRNAs with relevant as diagnostic markers for NAFLD or NASH. Thus, circulating miRNAs show potential as biomarkers of fatty liver disease, but more information about phenotype specificity and longitudinal regulation is needed.

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“…One of the proposed roles of Spock1 is to regulate matrix metalloproteinase (MMP) activation, specifically gelatinases MMP-2 and MMP-9 (Du et al, 2020;Edgell et al, 2004;Nakada et al, 2001;Váncza et al, 2022;Ye et al, 2020). To assess whether spock1 hm41/hm41 mutants had altered gelatinase activity that corresponded to observed changes in vascular cell interactions, we performed in vivo gelatin zymography by intracranial injections of highly quenched FITC-gelatin.…”

Section: Mutant Leakage Arises From Increased Transcytosis and Altere...mentioning

confidence: 99%

The secreted neuronal signal Spock1 regulates the blood-brain barrier

O'Brown

Patel

Hartmann

et al. 2021

Preprint

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The blood-brain barrier (BBB) is comprised of a single layer of endothelial cells with uniquely restrictive properties required for maintaining a tightly controlled homeostatic environment in the brain. Classic quail-chick grafting experiments showed that BBB properties are not intrinsic to brain endothelial cells, but instead are induced by signals from the embryonic brain microenvironment. Here we have identified a neuronally produced signal, Spock1, that specifically regulates BBB functional development in both zebrafish and mice without affecting angiogenesis. Using a combination of mosaic genetic analysis, tracer leakage assays and live imaging we show that Spock1 from neurons can regulate brain vasculature permeability non-cell autonomously. Electron microscopy analyses of spock1 mutants revealed that the leakage arises predominantly through increased endothelial transcytosis of both clathrin-independent small and large vesicles due to altered pericyte-endothelial interactions. Single-cell RNA sequencing analyses revealed a reduction in vascular expression of the cell adhesion molecule mcamb in the spock1 mutants, and this down-regulation of mcamb occurred specifically in regions with increased BBB leakage. These analyses indicate that the neuronal signal Spock1 regulates BBB properties by altering vascular gene expression and cellular interactions.

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SPOCK1 with unexpected function. The start of a new career

Cited by 8 publications

References 52 publications

SPOCK1 Overexpression Suggests Poor Prognosis of Ovarian Cancer

SPOCK1 Overexpression Suggests Poor Prognosis of Ovarian Cancer

Circulating miRNAs associated with nonalcoholic fatty liver disease

The secreted neuronal signal Spock1 regulates the blood-brain barrier

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