Conflicting Views on the Molecular Structure of the Cancer Antigen CA125/MUC16

Bouanene, Houda; Miled, Abdelhédi

doi:10.1155/2010/918457

Cited by 25 publications

(14 citation statements)

References 65 publications

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“…Besides APC , both 1stDCGs and 2ndDCGs contain known cancer genes with many already being targeted for therapeutic intervention, including the DNA damage-inducible cell-cycle regulator GADD45A (22), the constitutive glucose transporter SLC2A1 (23), the signaling molecule A3 adenosine receptor ADORA3 (24), the chromatin modifier EZH2 (6), the receptor tyrosine phosphatase PTPRD (25), and the cancer biomarker MUC16 (26). The PCGs, however, do not contain any such genes.…”

Section: Resultsmentioning

confidence: 99%

Cancer driver–passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer

Tang

Lyon

et al. 2013

Oncogene

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Herein we report a proof of principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver–passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human- and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, while PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A, and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.

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Section: Resultsmentioning

confidence: 99%

Cancer driver–passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer

Tang

Lyon

et al. 2013

Oncogene

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“…The reliability of first generation ELISA to determine CA125 levels is therefore doubtful. All together, the findings explain the conflicting reports on the molecular structure of CA125 (reviewed in [20]) and also the inconsistencies of CA125 levels measured by different ELISAs [3]. …”

Section: Introductionmentioning

confidence: 64%

Methods for Identification of CA125 from Ovarian Cancer Ascites by High Resolution Mass Spectrometry

Weiland

Fritz

Oehler

et al. 2012

IJMS

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CA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory sensitivity and specificity especially at early stage. It is quantified by antibody-based immunoassays; however different molecular weight isoforms have been described in the literature which have never been validated by mass spectrometry, potentially affecting the diagnostic accuracy and clinical reliability of the test. In this study, CA125 was detected by Western blot and its identity confirmed by mass spectrometry. Two-dimensional (2D) gel electrophoresis in combination with mass spectrometry revealed that positive Western blot signals up to 500 kDa are most likely false-positive interactions of M11-like and OC125-like antibodies. Fibronectin, identified as one of these false-positive interaction partners, increased the reading for CA125 in a first generation ELISA significantly (p = 0.02). The existence of low-molecular weight isoforms of CA125 is therefore questionable and is most likely reflecting cross-reactivity of the antibodies with other proteins. This would explain the conflicting reports on the molecular structure of CA125 and also the inconsistency of CA125 levels by different ELISAs. Our results are also the first steps towards a mass spectrometric assay for CA125 quantification, which would improve sensitivity and reliability.

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“…This may be because the NK synaptic cleft requires a distance of 10–50 nm between NK and cancer cells, which is thought to be disrupted by the large (up to 24,000 amino acid) protein backbone of CA125 that can protrude from ovarian tumor cells by up to 1–5μm. 5 However, given the heterogeneity of the size of CA125 reported, which may be a result of the biological source of the molecules studied or differing biological methods used to characterize them, 6 or significant variation in the extent of protein glycosylation, 5 the degree of immune escape as well as other biological functions of CA125-expressing tumor cells may vary.…”

Section: Targets For Antibody Treatmentsmentioning

confidence: 99%

Therapeutic targets and new directions for antibodies developed for ovarian cancer

Bax

Josephs

Pellizzari

et al. 2016

mAbs

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Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets. In turn, potential antibody treatments with various mechanisms of action, including immune activation or toxin-delivery, that are directed at these targets have been developed. Here, we identify established as well as novel targets for antibodies in ovarian cancer, and discuss how they may provide fresh opportunities to identify interventions with enhanced therapeutic potential.

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Conflicting Views on the Molecular Structure of the Cancer Antigen CA125/MUC16

Cited by 25 publications

References 65 publications

Cancer driver–passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer

Cancer driver–passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer

Methods for Identification of CA125 from Ovarian Cancer Ascites by High Resolution Mass Spectrometry

Therapeutic targets and new directions for antibodies developed for ovarian cancer

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