BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin < 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment.

2023-01-01·Methods in molecular biology (Clifton, N.J.)

Evaluation of the In Vitro and In Vivo Effects of Biglycan in Innate Immunity

Article

作者: Wygrecka, Malgorzata ; Huber, Lisa Sophie ; Zeng-Brouwers, Jinyang ; Trebicka, Jonel ; Schaefer, Liliana ; Merline, Rosetta

Biglycan, a small leucine-rich proteoglycan (SLRP), is a crucial component of the extracellular matrix (ECM) associated with the maintenance of tissue homeostasis. In response to tissue damage, the ECM-derived soluble form of biglycan acts as a danger signal by triggering an inflammatory response via the toll-like receptor (TLR)2/TLR4 in macrophages and dendritic cells. The impact and signaling mechanism of biglycan in innate immunity is better understood with the use of specific and reliable research tools and investigation techniques. Accordingly, our lab has established explicit and detailed experimental protocols to examine the in vitro and in vivo effects of biglycan in cellular immune responses. To evaluate the in vitro effects of biglycan on macrophage activation, a comprehensive protocol that makes use of murine peritoneal macrophages has been described. Further, to study the in vivo effects of biglycan, a method that uses a pLIVE vector to generate transgenic mice transiently overexpressing human biglycan is detailed. A step-by-step protocol for analyzing the effects of soluble biglycan overexpression in transgenic mice is explained under the following sections: (1) construction of pLIVE-hBGN plasmid, (2) intravenous delivery of transgenic vector, (3) identification of hBGN transgene in hepatocytes (4) detection of transgenic biglycan protein in the plasma of transgenic mice, and (5) evaluation of the presence and pro-inflammatory effects of transgenic biglycan in extrahepatic mouse tissues.

2022-12-01·American journal of physiology. Cell physiology

Rapamycin-induced autophagy in osteosarcoma cells is mediated via the biglycan/Wnt/β-catenin signaling axis

Article

作者: Samsonov, Sergey A. ; Tsatsakis, Aristidis M. ; Gaardløs, Margrethe ; Nikitovic, Dragana ; Berdiaki, Aikaterini ; Giatagana, Eirini-Maria

Biglycan is a class I secreted small leucine-rich proteoglycan (SLRP), which regulates signaling pathways connected to bone pathologies. Autophagy is a vital catabolic process with a dual role in cancer progression. Here, we show that biglycan inhibits autophagy in two osteosarcoma cell lines ( P ≤ 0.001), while rapamycin-induced autophagy decreases biglycan expression in MG63 osteosarcoma cells and abrogates the biglycan-induced cell growth increase ( P ≤ 0.001). Rapamycin also inhibits β-catenin translocation to the nucleus, inhibiting the Wnt pathway ( P ≤ 0.001) and reducing biglycan’s colocalization with the Wnt coreceptor LRP6 ( P ≤ 0.05). Furthermore, biglycan exhibits protective effects against the chemotherapeutic drug doxorubicin in MG63 OS cells through an autophagy-dependent manner ( P ≤ 0.05). Cotreatment of these cells with rapamycin and doxorubicin enhances cells response to doxorubicin by decreasing biglycan ( P ≤ 0.001) and β-catenin ( P ≤ 0.05) expression. Biglycan deficiency leads to increased caspase-3 activation ( P ≤ 0.05), suggesting increased apoptosis of biglycan-deficient cells treated with doxorubicin. Computational models of LRP6 and biglycan complexes suggest that biglycan changes the receptor’s ability to interact with other signaling molecules by affecting the interdomain bending angles in the receptor structure. Biglycan binding to LRP6 activates the Wnt pathway and β-catenin nuclear translocation by disrupting β-catenin degradation complex ( P ≤ 0.01 and P ≤ 0.05). Interestingly, this mechanism is not followed in moderately differentiated, biglycan-nonexpressing U-2OS OS cells. To sum up, biglycan exhibits protective effects against the doxorubicin in MG63 OS cells by activating the Wnt signaling pathway and inhibiting autophagy.

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