Fetuin‐A (alpha 2<scp>HS</scp> glycoprotein) modulates growth, motility, invasion, and senescence in high‐grade astrocytomas

Nangami, Gladys N.; Sakwe, Amos M.; Izban, Michael G.; Rana, Tanu; Lammers, Philip E.; Thomas, Portia L.; Chen, Zhenbang; Ochieng, Josiah

doi:10.1002/cam4.940

Cited by 17 publications

(21 citation statements)

References 42 publications

(61 reference statements)

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“…Fetuin-A affects insulin resistance, which is associated with increased risk of cancer. The progression of several cancers, such as pancreatic cancer,43 prostate cancer,23 and glioblastoma multiforme,44 is driven by synthesis of ectopic fetuin-A. Research has shown that a higher level of fetuin-A is associated with a modestly higher risk of colorectal cancer 45.…”

Section: Discussionmentioning

confidence: 99%

<p>Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression And Prognosis Of Chondrosarcoma</p>

Shi

Liu

et al. 2019

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AimsChondrosarcoma (CS) is a high-morbidity, relatively common bone malignancy without well-established biomarkers. The proteins EAAT1, DHFR, and fetuin-A have been investigated in many cancers, but their specific relationship to CS has not been reported. The present study examined EAAT1, DHFR, and fetuin-A expression in CS and the clinicopathological significance of these proteins in CS pathogenesis, progression, and prognosis.MethodsEAAT1, DHFR, and fetuin-A protein levels in 80 CS and 25 chondroma specimens were measured by immunohistochemistry and related to histological and clinical factors with chi-squared tests. Following univariate survival analysis, ROC curves calculation, and multivariate analysis.ResultsEAAT1, DHFR, and fetuin-A expression levels were significantly higher in the CS group than in the chondroma group (p < 0.05). Their immunopositivity rates were significantly greater in tissues with moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, and metastasis (p<0.05 or p<0.01 or p<0.001). Kaplan–Meier survival analysis showed significantly shorter survival in patients with moderately or poorly differentiated tumors, AJCC stage III or IV CS, Enneking stage II or III CS, metastasis, invasion, or EAAT1, DHFR, and fetuin-A immunopositivity (p < 0.05 or p < 0.001). Cox regression analysis showed that moderate or poor tumor differentiation, AJCC stage III or IV, Enneking stage II or III, metastasis, invasion, and EAAT1, DHFR, or fetuin-A immunopositivity correlated negatively with postoperative survival and positively with mortality (p < 0.05). The AUCs for EAAT1, DHFR, and fetuin-A were 0.654 (95% CI: 0.532–0.776, p = 0.025), 0.638 (95% CI: 0.519–0.756, p = 0.039), and 0.670 (95% CI: 0.556–0.784, p = 0.011), respectively.ConclusionEAAT1, DHFR, and fetuin-A may be important biomarkers of the pathogenesis and progression of CS and predictors of its prognosis.

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Section: Discussionmentioning

confidence: 99%

<p>Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression And Prognosis Of Chondrosarcoma</p>

Shi

Liu

et al. 2019

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“…The rapid uptake of fetuin-A by adherent tumor cells is necessary for their growth and survival. Reduced levels or absence of fetuin-A in the growth media or tumor microenvironment results in slow and poor growth of tumor cells in vitro and in vivo [3,4,11]. Fetuin-A mediates optimal cellular adhesion and spreading on various substrata not only in vitro but also in vivo, thereby promoting anchorage-dependent cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

The rapid endocytic uptake of fetuin‐A by adherent tumor cells is mediated by Toll‐like receptor 4 (TLR4)

et al. 2020

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The study demonstrates that TLR4 mediates the rapid uptake of fetuin‐A by tumor cells to promote rapid adhesion, spreading, growth, motility, and invasion in serum‐free medium. The specific TLR4 inhibitor, CLI‐095, inhibits rapid fetuin‐A uptake, and consequently, most tumor cells, particularly those that do not synthesize fetuin‐A, fail to adhere, spread, or grow in serum‐free medium.

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“…As noted, nearly all the circulating fetuin‐A in CPP is in the phosphorylated state . Apart from its major role, fetuin‐A can also function as an oncogenic protein by promoting cell growth, adhesion, motility, and invasion of cancer cells . More recently, a number of studies have demonstrated that fetuin‐A is involved in the biogenesis of tumor exosome by accelerating the secretion of exosomes.…”

Section: Discussionmentioning

confidence: 99%

Phosphoproteome Profiling of Isogenic Cancer Cell‐Derived Exosome Reveals HSP90 as a Potential Marker for Human Cholangiocarcinoma

et al. 2019

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The northeastern region of Thailand is well known to have a high incidence and mortality of cholangiocarcinoma (CCA). Protein phosphorylation status has been reported to reflect a key determinant of cellular physiology, but identification of phosphoproteins can be a problem due to the presence of phosphatase. Exosomes are stable toward circulating proteases and other enzymes in human blood and can be recognized before the onset of cancer progression. Here an in vitro metastatic model of isogenic CCA cells is used to provide insight into the phosphorylation levels of exosomal proteins derived from highly invasive cells. Gel-based and gel-free proteomics approaches are used to reveal the proteins differentially phosphorylated in relation to tumor cell phenotypes. Forty-three phosphoproteins are identified with a significant change in phosphorylation level. Phos-tag western blotting and immunohistochemistry staining are then employed to validate the candidate phosphoproteins. Heat shock protein 90 is successfully confirmed as being differentially phosphorylated in relation to tumor malignancy.

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Fetuin‐A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high‐grade astrocytomas

Cited by 17 publications

References 42 publications

<p>Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression And Prognosis Of Chondrosarcoma</p>

<p>Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression And Prognosis Of Chondrosarcoma</p>

The rapid endocytic uptake of fetuin‐A by adherent tumor cells is mediated by Toll‐like receptor 4 (TLR4)

Phosphoproteome Profiling of Isogenic Cancer Cell‐Derived Exosome Reveals HSP90 as a Potential Marker for Human Cholangiocarcinoma

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