The significance of lumican expression in ovarian cancer drug-resistant cell lines

Klejewski, Andrzej; Sterzyńska, Karolina; Wójtowicz, Karolina; Świerczewska, Monika; Partyka, Małgorzata; Brązert, Maciej; Nowicki, Michał; Zabel, Maciej

doi:10.18632/oncotarget.20169

Cited by 27 publications

(36 citation statements)

References 40 publications

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“…In the cornea, lumican is expressed as the keratin sulfate proteoglycan, and is considered to possess the heterogeneous glycosaminoglycan [ 32 , 35 ]. Previously, various molecular weights of lumican between 37 and 250 kDa due to differences in glycosylation were detected from cell extracts by Western blot [ 36 , 37 , 38 , 39 , 40 ]. Our results also showed that various molecular weights of lumican between 37 and 250 kDa were observed in the cornea of rat, and increased lumican expression was observed in the cornea of the STZ rat (STZ) as compared to in that of the normal rat (Normal) ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Yamamoto

Otake

Hiramatsu

et al. 2018

IJMS

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Diabetes mellitus is a widespread metabolic disorder, and long-term hyperglycemia in diabetics leads to diabetic keratopathy. In the present study, we used a shotgun liquid chromatography/mass spectrometry-based global proteomic approach using the cornea of streptozotocin-induced diabetic (STZ) rats to examine the mechanisms of delayed corneal wound healing in diabetic keratopathy. Applying a label-free quantitation method based on spectral counting, we identified 188 proteins that showed expression changes of >2.0-fold in the cornea of STZ rats. In particular, the level of lumican expression in the cornea of STZ rats was higher than that of the normal rats. In the cornea of the normal rat, the expression level of lumican was elevated during the wound healing process, and it returned to the same expression level as before cornea injury after the wound was healed completely. On the other hand, a high expression level of lumican in the cornea of STZ rats was still maintained even after the wound was healed completely. In addition, adhesion deficiency in corneal basal cells and Bowman’s membrane was observed in the STZ rat. Thus, abnormally overexpressed lumican may lead to adhesion deficiency in the cornea of STZ rats.

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Section: Resultsmentioning

confidence: 99%

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

Yamamoto

Otake

Hiramatsu

et al. 2018

IJMS

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“…However, an increasing body of evidence indicates that expression of ECM proteins in the tumor environment can play even more important role in drug resistance, especially from the clinical point of view [ 10 , 39 ]. It is worth mentioning that expression of ECM and related proteins is limited not only to tumor stroma and cancer-associated fibroblasts (CAF) but was also observed in tumor cells in vivo [ 10 , 12 , 15 , 40 , 41 ] and in cancer cell lines [ 13 , 37 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…This form was overexpressed in cell lines resistant to PAC and TOP. Since we previously observed that COL3A1, LUM [ 14 , 15 ] and MYOT (under review) are secreted to cell culture media in drug resistant ovarian cancer cell lines, we were interested whether MGP can also be present in the culture medium. Indeed, we have noticed that MGP protein was present in culture media from investigated drug resistant cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were cultured on microscopic glass slides and grown to a near-confluent state. Immunofluorescence analysis was conducted following the previously established protocol [ 15 ]. Briefly, the cells were fixed with 4% PFA, permeabilized in ice-cold acetone/methanol (1:1) and then washed with PBS.…”

Section: Methodsmentioning

confidence: 99%

“…Cancer cells show decreased sensitivity to apoptosis influenced by ECM components that leads to induction of their resistance [ 9 ]. The development of drug resistance caused by compounds of extracellular matrix has been described as cell adhesion-mediated drug resistance (CAM-DR) [ 10 ] and noted in small cell lung cancer in vivo and in ovarian cancer in vitro [ 11 , 12 ] However, different molecules of ECM have also been described as produced by cultured cells in vitro, e.g., drug resistant breast [ 13 ] and ovarian cancer cell lines [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines

Sterzyńska

Klejewski

Wójtowicz

et al. 2018

IJMS

Self Cite

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The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. MGP mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.

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The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia

Liu

Wang

et al. 2021

Reprod. Sci.

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Multiple pieces of evidence illustrate that impaired trophoblast function results in preeclampsia (PE), and migration/invasion of human trophoblast cells is stringently regulated by extracellular matrix (ECM) components. Many studies have indicated abnormal expressions of placental ECM components are associated with preeclampsia. However, the change and influence of lumican, a vital member of extracellular matrix (ECM) molecules, on trophoblast cells during preeclampsia remain unclear. This study examines the possibility that the roles of lumican in trophoblast cells contribute to PE. To address this issue, the expression of lumican in human placental tissues was observed using immunohistochemistry, fluorescence quantitative PCR, and Western blot technology. After the HTR-8/SVneo cell line was transfected with pcDNA3.1-human lumican, pGPU6-human lumican shRNA, and their negative controls, the impact of lumican on the HTR-8/SVneo cell line was investigated. Lumican was expressed in human placental tissues. Compared with the control group, its expression was significantly lower in PE placentas. Lumican downregulation inhibited cell proliferation significantly and reduced Bcl-2 expression, but increased P53 expression. These results indicate that the downregulation of placental lumican may drive PE development via promoting the downregulation of Bcl-2 expression and upregulation of P53.

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The significance of lumican expression in ovarian cancer drug-resistant cell lines

Cited by 27 publications

References 40 publications

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

A Proteomic Approach for Understanding the Mechanisms of Delayed Corneal Wound Healing in Diabetic Keratopathy Using Diabetic Model Rat

The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines

The Downregulation of Placental Lumican Promotes the Progression of Preeclampsia

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