scholarly journals Sulfation of O-glycans on mucin-type proteins from serous ovarian epithelial tumors

Author(s):  
Kristina Thomsson Hulthe ◽  
Varvara Vitiazeva ◽  
Constantina Mateoiu ◽  
Chunsheng Jin ◽  
Jining Liu ◽  
...  

Despite that sulfated O-linked glycans are abundant on ovarian cancer (OC) glycoproteins, their regulation during cancer development and involvement in cancer pathogenesis remain unexplored. We characterized O-glycans carrying sulfation on galactose residues and compared their expression to defined sulfotransferases regulated during OC development. Desialylated sulfated oligosaccharides were released from acidic glycoproteins in the cyst fluid from one patient with a benign serous cyst and one patient with serous OC. Oligosaccharides characterized by LC-MSn were identified as core 1 and core 2 O-glycans up to the size of decamers, and with 1-4 sulfates linked to GlcNAc residues and to C-3 and/or C-6 of Gal. To study the specificity of the potential ovarian sulfotransferases involved, Gal3ST2 (Gal-3S)-, Gal3ST4 (Gal-3S)-, and CHST1 (Gal-6S)-encoding expression plasmids were transfected individually into CHO cells also expressing the P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b (PSGL-1/mIg G2b) fusion protein and the human core 2 transferase (GCNT1). Characterization of the PSGL-1/mIg G2b O-glycans showed that Gal3ST2 preferentially sulfated Gal on the C-6 branch of core 2 structures and Gal3ST4 preferred Gal on the C-3 branch independently if core-1 or-2. CHST1 sulfated Gal residues on both the C-3 (core 1/2) and C-6 branches of core 2 structures. Using serous ovarian tissue micro array, Gal3ST2 was found to be decreased in tissue classified as malignant compared to tissues classified as benign or borderline, with the lowest expression in poorly differentiated malignant tissue. Neither Gal3ST4 nor CHST1 were differentially expressed in benign, borderline or malignant tissue, and there was no correlation between expression level and differentiation stage. The data displays a complex sulfation pattern of O-glycans on OC glycoproteins and that aggressiveness of the cancer is associated with a decreased expression of the Gal3ST2 transferase.

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3523
Author(s):  
Wancheng Guo ◽  
Haiqin Wang ◽  
Peng Chen ◽  
Xiaokai Shen ◽  
Boxin Zhang ◽  
...  

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Zhiqiang Qin ◽  
Andrew Jakymiw ◽  
Victoria Findlay ◽  
Chris Parsons

The human genome contains microRNAs (miRNAs), small noncoding RNAs that orchestrate a number of physiologic processes through regulation of gene expression. Burgeoning evidence suggests that dysregulation of miRNAs may promote disease progression and cancer pathogenesis. Virus-encoded miRNAs, exhibiting unique molecular signatures and functions, have been increasingly recognized as contributors to viral cancer pathogenesis. A large segment of the existing knowledge in this area has been generated through characterization of miRNAs encoded by the human gamma-herpesviruses, including the Kaposi’s sarcoma-associated herpesvirus (KSHV). Recent studies focusing on KSHV miRNAs have led to a better understanding of viral miRNA expression in human tumors, the identification of novel pathologic check points regulated by viral miRNAs, and new insights for viral miRNA interactions with cellular (“human”) miRNAs. Elucidating the functional effects of inhibiting KSHV miRNAs has also provided a foundation for further translational efforts and consideration of clinical applications. This paper summarizes recent literature outlining mechanisms for KSHV miRNA regulation of cellular function and cancer-associated pathogenesis, as well as implications for interactions between KSHV and human miRNAs that may facilitate cancer progression. Finally, insights are offered for the clinical feasibility of targeting miRNAs as a therapeutic approach for viral cancers.


Author(s):  
Peter J. Schüffler ◽  
Thomas J. Fuchs ◽  
Cheng Soon Ong ◽  
Volker Roth ◽  
Joachim M. Buhmann

2011 ◽  
Vol 299-300 ◽  
pp. 1128-1131
Author(s):  
Yu Cheng Zhang

Against the problem on poor quality and inefficiency in the preparation of bio tissue micro array by hand, the one processing system of biotissue micro-array was developed. The application of NC image identification technology was made to carry out auto punching, auto-positioning- embedding, and auto-extracting, etc. The auto preparation of biotissue micro array was completed. The adoption of the minimum squares fitting was aimed at object’s primes to be fitted so as to obtain special-feature parameters to finish accurate position and auto rectification of deviation visual view range in micro-hole image. There by, visual deviation operated by hand was avoided and highlighted the processed accuracy.


2001 ◽  
Vol 29 (2) ◽  
pp. 128-135 ◽  
Author(s):  
Molly Brewer ◽  
Urs Utzinger ◽  
Elvio Silva ◽  
David Gershenson ◽  
Robert C. Bast ◽  
...  

Materials ◽  
2020 ◽  
Vol 13 (17) ◽  
pp. 3759
Author(s):  
Giulia Pascoletti ◽  
Maddalena Di Nardo ◽  
Gionata Fragomeni ◽  
Vincenza Barbato ◽  
Teresa Capriglione ◽  
...  

The ovary is a dynamic mechanoresponsive organ. In vitro, tissue biomechanics was reported to affect follicle activation mainly through the Hippo pathway. Only recently, ovary responsiveness to mechanical signals was exploited for reproductive purposes. Unfortunately, poor characterization of ovarian cortex biomechanics and of the mechanical challenge hampers reproducible and effective treatments, and prevention of tissue damages. In this study the biomechanical response of ovarian cortical tissue from abattoir bovines was characterized for the first time. Ovarian cortical tissue fragments were subjected to uniaxial dynamic testing at frequencies up to 30 Hz, and at increasing average stresses. Tissue structure prior to and after testing was characterized by histology, with established fixation and staining protocols, to assess follicle quality and stage. Tissue properties largely varied with the donor. Bovine ovarian cortical tissue consistently exhibited a nonlinear viscoelastic behavior, with dominant elastic characteristics, in the low range of other reproductive tissues, and significant creep. Strain rate was independent of the applied stress. Histological analysis prior to and after mechanical tests showed that the short-term dynamic mechanical test used for the study did not cause significant tissue tear, nor follicle expulsion or cell damage.


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