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Mother and Embryo Cross Communication during Conception
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Anna Idelevich, Andrea Peralta, Felipe Vilella
Mucin 1 (MUC 1), a highly glycosylated, polymorphic, mucin-like protein, is secreted by the endometrial luminal epithelium. It is considered to be a “barrier to implantation.” In humans, it was shown to be expressed in the luteal phase and pre-implantation phase in a progesterone-dependent manner [103–105]. MUC 1 is more abundant in fertile than in infertile women [106]. In baboons, it was also shown to be progesterone- rather than estrogen-dependent, serving as a marker of the pre-implantation phase [107]. Of interest is a recent study investigating similarity between term pregnancy in marsupials and eutherian mammals, which found that key markers of implantation, including Mucin 1, heparin-binding EGF-like factor (HBEGF), and a range of proinflammatory factors, including IL-6, tumor necrosis factor (TNF), and cyclooxygenase 2 (COX2), are consistent between species and embryo implantation has been suggested. There are transcriptome-wide similarities between the marsupial attachment reaction and implantation in rabbits and humans [108]. Specifically, the marsupial study observed an overlap in the key implantation biomarker osteopontin, which is the only consistent implantation window biomarker identified from five human microarray experiments [109].
Use of Molecular Markers of Endometrial Receptivity
Published in Botros Rizk, Yakoub Khalaf, Controversies in Assisted Reproduction, 2020
Alejandro Rincón, David Bolumar, Diana Valbuena, Carlos Simón
During the same year, antiadhesion molecules were being studied, specifically mucin 1 (MUC-1). The associated cell surface is a highly glycosylated high molecular weight protein glycocalyx that covers luminal epithelium cells, forming a gel-like secretion. For this reason, mucins indirectly protect cells from pathogen infection, avoiding cell surface–pathogen contact and later putative adhesion. MUC-1 is overexpressed around 36 hours following the luteinizing hormone (LH) peak (20), and its deposition avoids cell areas covered by pinopods, favoring blastocyst implantation.
Chimeric VLPs
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The CuAAC reaction was also used recently to construct a putative anticancer vaccine candidate (Yin Z et al. 2018). Thus, the mucin-1, one of the top ranked tumor associated antigens, was displayed on the Qβ VLPs. The mucin-1 peptides and glycopeptides were covalently conjugated to the Qβ VLPs. The immunization of mice with these constructs led to highly potent antibody responses with IgG titers over one million, which were among the highest anti-mucin-1 IgG titers reported to date. The high IgG antibody levels persisted for more than 6 months. The constructs also elicited mucin-1 specific cytotoxic T cells, which selectively killed mucin-1 positive tumor cells. The unique abilities of the Qβ-mucin-1 conjugates to powerfully induce both antibody and cytotoxic T cell immunity targeting tumor cells therefore bode well for the future translation of the constructs as anticancer vaccines (Yin Z et al. 2018).
Therapeutic challenges at the preclinical level for targeted drug development for Opisthorchis viverrini-associated cholangiocarcinoma
Published in Expert Opinion on Investigational Drugs, 2021
Watcharin Loilome, Hasaya Dokduang, Manida Suksawat, Sureerat Padthaisong
Another promising immunotherapy approach in Ov-related CCA is using adoptive T cell transfer using chimeric antigen receptor (CAR) T cells which can recognize specific surface antigen without major MHC restriction [148]. Selection of suitable antigens on cancer cells is essential for designing an effective CAR T cell approach and avoidance of side effects. Mucin 1 (MUC1) is the convincing candidate antigen which highly expressed and associated with poor prognosis and survival in CCA [149]. The recent study [150] has established anti-MUC1-CAR4 and used lentiviral vector and introduced into human T cells, anti- MUC1-CAR4 T cell showed anti-cancer activity against MUC1-expressing CCA cells by enhanced anti-tumor cytokines (TNF-α and IFN-γ) and pro-apoptotic protein (granzyme B) production and induced CCA cell lysis both in 2D and 3D (spheroid) co-cultures. Regarding to improve specificity of CAR T cell against CCA cell, they also created CAR T cells targeting integrin αvβ6 which overexpression in CCA tissues and correlated with poor survival of CCA patient. CAR T cells targeting integrin αvβ6 was established by engineered lentivirus encode CARs containing an integrin αvβ6-binding peptide and delivery to T cell. The results revealed that this can promote cytotoxicity and showed anti- tumor activity on of CAR T cell against integrin αvβ6-positive CCA cell [151].
Glycosylation and its implications in breast cancer
Published in Expert Review of Proteomics, 2019
Danielle A. Scott, Richard R. Drake
The most common types of O-glycan structures detected in breast cancer and many other cancer types is Tn-antigen, sialyl-Tn, and Thomsen-Friedenreich antigen (see Figure 3) [79–88]. These structures are most commonly associated with mucin-glycoproteins, and the enzymes responsible for mucin-type O-glycosylation initiation also exhibit altered expression in cancer. These polypeptide GalNAc transferases control O-glycan occupancy sites, and the density with which these sites can be occupied [89–91]. Furthermore, multiple enzymes competing for the same substrates can also result in O-glycan truncation [92]. Elevation of Mucin-1 (MUC-1) has been noted in breast cancers for many years. MUC-1 is a large transmembrane protein that is carrier of aberrant O-glycosylation in tumor cells. Changes in aberrant O-glycosylation of MUC-1 result in the exposure of the protein core, allowing cells to adhere to distant tissues and resulting in metastasis [75,90]. Furthermore, when MUC-1 is under-glycosylated, this is associated with higher tumor grades and poor prognosis [93].
Changes in mucin 1 expression in a rat model of allergic airway inflammation
Published in Experimental Lung Research, 2018
Bilal Hasan, Haimiti Abudulimu, Li Tian, Abduxukur Ablimit
Bronchial asthma (asthma) is a common chronic respiratory disease showing increased prevalence and mortality rates.1,2 Asthmatic episodes are characterized by allergic airway inflammation, airway hyperreactivity, mucus hypersecretion and airway remodeling.3,4 Mucin 1 (MUC1 in human beings or Muc1 in animals) mainly distributes in epithelial tissues, such as the airway, breast, gastrointestinal tract and urogenital tract.5 Although MUC1/Muc1 is abundantly expressed in the lung epithelia like type II alveolar cells, studies of its distribution in airway epithelial cells have been inconclusive.6 The functions of MUC1/Muc1 include cell protection, lubrication and immune regulation.7–9 In airway, Muc1 has been suggested to act as a suppressor of inflammation caused by bacterial and viral infections in the upper respiratory tract.9,10 The negatively regulatory effects of Muc1 on toll-like receptor signaling are responsible for these anti-inflammatory functions.11 The cytokines secreted by airway epithelial cells, which are controlled by TLR mediated signaling, play pivotal roles in the occurrence and progression of asthma.12–14 Although the association between mucin 1 and asthma or allergic inflammatory responses in airway are need to be identified, a clinical study showed that serum level of KL-6, one of the MUC1 antigens, was increased in pediatric asthma patients under exacerbation.15