scholarly journals A Disintegrin and Metalloproteinase 9 Is Involved in Ectodomain Shedding of Receptor-Binding Cancer Antigen Expressed on SiSo Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Kenzo Sonoda ◽  
Kiyoko Kato
Keyword(s):  
Receptor Binding ◽  
Uterine Cancer ◽  
Proteolytic Processing ◽  
Soluble Form ◽  
Ectodomain Shedding ◽  
Cancer Antigen ◽  
Poor Overall Survival ◽  
A Disintegrin And Metalloproteinase ◽  
Metalloproteinase 9 ◽  
Protease Expression

In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. RCAS1 alters the tumor microenvironment by inducing peripheral lymphocyte apoptosis and angiogenesis, while reducing the vimentin-positive cell population. Although proteolytic processing, referred to as “ectodomain shedding,” is pivotal for induction of apoptosis by RCAS1, the proteases involved in RCAS1-dependent shedding remain unclear. Here we investigated proteases involved in RCAS1 shedding and the association between tumor protease expression and serum RCAS1 concentration in uterine cancer patients. A disintegrin and metalloproteinase (ADAM) 9 was shown to be involved in the ectodomain shedding of RCAS1. Given the significant correlation between tumor ADAM9 expression and serum RCAS1 concentration in both cervical and endometrial cancer as well as the role for ADAM9 in RCAS1 shedding, further exploration of the regulatory mechanisms by which ADAM9 converts membrane-anchored RCAS1 into its soluble form should aid the development of novel RCAS1-targeting therapeutic strategies to treat human malignancies.

scholarly journals Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer

Cancer ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 1979-1990 ◽  
Author(s):  
Kenzo Sonoda ◽  
Shingo Miyamoto ◽  
Ayano Yamazaki ◽  
Hiroaki Kobayashi ◽  
Manabu Nakashima ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Receptor Binding ◽  
Uterine Cancer ◽  
Cancer Antigen

Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells

Blood ◽  
2001 ◽  
Vol 98 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Takamitsu Matsushima ◽  
Manabu Nakashima ◽  
Koichi Oshima ◽  
Yasunobu Abe ◽  
Junji Nishimura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Receptor Binding ◽  
Transferrin Receptor ◽  
Human Peripheral Blood ◽  
Soluble Form ◽  
Glycophorin A ◽  
Cancer Antigen ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

To better understand the control of apoptosis during erythropoiesis, this study investigated the role of a novel tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells), with regard to the regulation of apoptosis of erythroid progenitor cells. Erythroid colony-forming cells (ECFCs) purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone marrow cells was analyzed, RCAS1R was evident on cells with an immature erythroid phenotype (transferrin receptor+/glycophorin A−) but not with a mature phenotype (transferrin receptor−/glycophorin A+). Histochemical staining revealed the expression of RCAS1 in the cytoplasm of bone marrow macrophages. These findings indicate that RCAS1, which is mainly produced by macrophages in hematopoietic tissue, may have a crucial role in controlling erythropoiesis by modulating apoptosis of erythroid progenitor cells via a Fas-independent mechanism.

scholarly journals Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding

2010 ◽  
Vol 316 (11) ◽  
pp. 1795-1803 ◽  
Author(s):  
Kenzo Sonoda ◽  
Shingo Miyamoto ◽  
Manabu Nakashima ◽  
Norio Wake
Keyword(s):  
Receptor Binding ◽  
Ectodomain Shedding ◽  
Cancer Antigen

scholarly journals Cancer antigen 125 is associated with disease status in uterine carcinosarcoma

Rare Tumors ◽  
2019 ◽  
Vol 11 ◽  
pp. 203636131988415
Author(s):  
Malcolm Strachan Ross ◽  
Chelsea Kilpatrick Chandler ◽  
Koji Matsuo ◽  
John Austin Vargo ◽  
Esther Elishaev ◽  
...  
Keyword(s):  
Overall Survival ◽  
Uterine Cancer ◽  
Disease Status ◽  
Post Treatment ◽  
Uterine Carcinosarcoma ◽  
Cancer Antigen 125 ◽  
Cancer Antigen ◽  
Time Points ◽  
Potential Biomarker ◽  
Significant Difference

Uterine carcinosarcoma is a rare and aggressive tumor with poor outcomes. Cancer antigen 125 is routinely used to track the disease course of ovarian cancer and has been suggested as a biomarker in other aggressive forms of uterine cancer. We sought to characterize cancer antigen 125 as a potential biomarker of disease status in uterine carcinosarcoma. Clinical and pathological data were abstracted for patients who had surgical staging for a pathologically confirmed uterine carcinosarcoma at our institution from January 2000 to March 2014. Non-parametric tests were used to compare changes in cancer antigen 125. Elevated cancer antigen 125 (>35 U/mL) as a predictor of survival was assessed via Kaplan–Meier curves. Among the 153 patients identified, 66 patients had at least one paired measure of cancer antigen 125 drawn preoperatively, post-treatment, or at the time of disease recurrence, and 19 patients had cancer antigen–125 levels at all three time points. Analysis of the 51 patients with both preoperative and post-treatment values found a significant drop in cancer antigen 125 ( p < 0.001). Among the 30 patients who had end-of-treatment and recurrence levels, a significant increase was noted ( p = 0.001). There was no significant difference in cancer antigen–125 levels preoperatively compared to at recurrence among the 23 patients with levels at both time-points ( p = 0.99). Elevated preoperative cancer antigen 125 was not associated with overall survival ( p = 0.12); elevated post-treatment cancer antigen 125 was associated with a worse overall survival ( p < 0.001). Based on this dataset, there seems to be utility in trending a cancer antigen–125 level in patients with uterine carcinosarcoma. A cancer antigen–125 level could predict recurrence and provide prognostic information regarding survival.

scholarly journals Sequential Proteolytic Processing of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Protein by Ectodomain Shedding and γ-Secretase-dependent Intramembranous Cleavage

2013 ◽  
Vol 288 (46) ◽  
pp. 33027-33036 ◽  
Author(s):  
Patrick Wunderlich ◽  
Konstantin Glebov ◽  
Nadja Kemmerling ◽  
Nguyen T. Tien ◽  
Harald Neumann ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Proteolytic Processing ◽  
Ectodomain Shedding

scholarly journals Broad Neutralization of Viral Pathogens

2014 ◽  
Vol 70 (a1) ◽  
pp. C245-C245
Author(s):  
Ian Wilson
Keyword(s):  
Hepatitis C ◽  
Binding Site ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Functional Characterization ◽  
Antigenic Site ◽  
Soluble Form ◽  
Receptor Binding Site ◽  
Fusion Domain ◽  
Hiv 1

Influenza, Hepatitis C, and HIV-1 continue to constitute significant threats to global health. We have structurally and functionally characterized several potent, broadly neutralizing antibodies (bnAbs) against HIV-1, influenza and hepatitis C viruses. The surface antigens of these viruses are the main target of neutralizing antibodies. However, most antibodies are strain-specific and protect only against highly related strains within the same subtype. Recently, a number of antibodies have been identified that are much broader and neutralize across multiple subtypes and types of these viruses through binding to functionally conserved sites, such as the receptor binding site or the fusion domain. For example, co-crystal structures of bnAbs with influenza hemagglutinin (HA) identified highly conserved sites in the fusion domain (stem) and in the receptor binding site (head) as target for broad neutralization[1]. HCV is also genetically diverse, but some antibodies have potent neutralizing activity across most genotypes of the virus. One family of these antibodies targets a conserved antigenic site on the HCV E2 envelope glycoprotein that overlaps with the CD81 receptor-binding site[2]. For HIV-1, structural and functional characterization of different families of bnAbs have led to identification of novel epitopes on HIV-1 Env, many of which involve glycans. These glycan-dependent Abs have unique features that enable them to penetrate the glycan shield and bind complex epitopes that consist of sugars and underlying protein segments on gp120 on HIV-1 Env. Recent x-ray[3] and EM structures of a soluble form of HIV-1 Env have revealed that the epitopes are more extensive and complex than previously appreciated. This structural information is now being used to aid in structure-assisted vaccine design for HIV-1, HCV and for a more universal flu vaccine. IAW is supported by NIH grants AI100663, AI082362, AI84817, AI099275 and GM094586 and the Crucell Vaccine Institute.

Diagnostic and Prognostic Utility of Serum Receptor-Binding Cancer Antigen Expressed on SiSo Cells (RCAS1) Levels in Colon Cancer Patients

2009 ◽  
Vol 24 (2) ◽  
pp. 70-76 ◽  
Author(s):  
Costas Giaginis ◽  
Alexandra Margeli ◽  
Gregory Kouraklis ◽  
Athina Zira ◽  
Gerasimos Tsourouflis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Receptor Binding ◽  
Univariate Analysis ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Cancer Antigen ◽  
Cox Regression Analysis ◽  
Prognostic Utility

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and/or apoptosis in cells bearing the RCAS1 receptor. The aim of the present study was to elucidate the diagnostic and prognostic utility of RCAS1 levels in colon cancer patients. Serum RCAS1 levels were determined using a sandwich enzyme-linked immunosorbent assay in 97 colon cancer patients and 20 healthy individuals. The levels were significantly increased in colon cancer patients compared to healthy individuals (p<0.0001). Increased RCAS1 levels were significantly associated with advanced Dukes’ stage (p=0.0079) and high histopathological tumor grade (p=0.0028). Univariate analysis revealed that colon cancer patients with elevated RCAS1 levels had significantly shorter overall survival times (log-rank test, p=0.027). By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (Cox regression analysis, p=0.033). In conclusion, colon cancer patients with advanced disease stage and grade and poor prognosis showed elevated serum RCAS1 levels. Assessment of serum RCAS1 levels could therefore be considered as a diagnostic and prognostic marker in colon neoplasia.

scholarly journals Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

2003 ◽  
Vol 163 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Satoru Yamazaki ◽  
Ryo Iwamoto ◽  
Kazuko Saeki ◽  
Masanori Asakura ◽  
Seiji Takashima ◽  
...  
Keyword(s):  
Heart Valves ◽  
Transmembrane Domain ◽  
Severe Heart Failure ◽  
Gene Replacement ◽  
Soluble Form ◽  
Ectodomain Shedding ◽  
Heparin Binding ◽  
Developmental Abnormalities ◽  
Targeted Gene Replacement

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain–truncated form (HBΔtm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBΔtm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control.

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