Synergistic growth inhibition and induction of apoptosis by a novel mixed backbone antisense oligonucleotide targeting CRIPTO in combination with C225 anti-EGFR monoclonal antibody and 8-Cl-cAMP in human GEO colon cancer cells.

Normanno, Nicola; Luca, Antonella De; Pomatico, G; Casamassimi, Amelia; Agrawal, Sudhir; Mendelsohn, John; Bianco, A. R.; Ciardiello, Fortunato

doi:10.3892/or.6.5.1105

Cited by 12 publications

(15 citation statements)

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“…This is supported by findings describing the use of antisense oligonucleotides that reduce Cripto-1 expression and cause significant reduction of cell proliferation in vitro [99]. In addition neutralizing antibodies against Cripto-1 [47] were able to significantly inhibit tumor cell growth in two xenograft models with testicular (NCCIT) and colon (GEO) cancer cells that express very high levels of Cripto-1 (Fig.…”

Section: Diagnostic and Therapeutic Applicationsupporting

confidence: 62%

“…5B). Moreover, rat monoclonal antibodies directed against the EGF-like domain of the Cripto-1 peptide also produced a significant inhibition of in vitro and in vivo growth of colon cancer and leukemia cells [99]. These results suggest that similar approaches for inhibiting cancer growth by interfering with expression or function of Cripto-1 may also have beneficial effects in Cripto-1 expressing breast cancer.…”

Section: Diagnostic and Therapeutic Applicationmentioning

confidence: 58%

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Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

Strizzi

Postovit

Margaryan

et al. 2008

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Breast carcinoma cells and embryonic progenitors similarly implement stem cell-associated signaling pathways to sustain continued growth and plasticity. Indeed, recent studies have implicated signaling pathways, including those associated with the Notch, and Transforming Growth Factor-Beta (TGF-β) superfamilies, as instrumental to both embryological development and breast cancer progression. In particular, Nodal, an embryonic morphogen belonging to the TGF-β superfamily, and its co-receptor, Cripto-1, are requisite to both embryogenesis and mammary gland maturation. Moreover, these developmental proteins have been shown to promote breast cancer progression. Here, we review the role of Nodal and its co-receptor Cripto-1 during development and we describe how this signaling pathway may be involved in breast cancer tumorigenesis. Moreover, we emphasize the potential utility of this signaling pathway as a novel target for the treatment and diagnosis of breast cancer.

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Section: Diagnostic and Therapeutic Applicationsupporting

confidence: 62%

Section: Diagnostic and Therapeutic Applicationmentioning

confidence: 58%

Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

Strizzi

Postovit

Margaryan

et al. 2008

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“…However, the combination of the three AS oligonucleotides each at 1 µM resulted in 60% inhibition of the AIG of the GEO cells. Similarly, an additive growth inhibitory effect was observed in MDA-MB-468 human breast cancer cells and in several different human ovarian carcinoma cell lines that had been treated with a combination of a CR-1 AS oligonucleotide and either a TGF AS or AR AS oligonucleotide (De Luca et al 1999, Casamassimi et al 2000. Provocative data have also been obtained using combinations of CR-1 AS oligonucleotides with conventional chemotherapeutic drugs in colon cancer cells (De Luca et al 1997).…”

Section: Cripto-1 As Target For Therapy In Human Cancermentioning

confidence: 74%

“…In a clonogenic assay, pretreatment of GEO cells with different concentrations of 5-fluorouracil, adriamycin, mitomycin C or cis-platinum induced an additive growth inhibitory effect when the cells were subsequently treated with a CR-1 AS oligonucleotide. More recently, CR-1 AS oligonucleotides have been used in combination with agents that block different but related intracellular signal transduction pathways (Normanno et al 1999). A novel mixed backbone CR-1 AS oligonucleotide has been used in combination with a humanized anti-human epidermal growth factor receptor antibody MAb C225 and with 8-Cl-cAMP, a specific analog that inhibits type I protein kinase A.…”

Section: Cripto-1 As Target For Therapy In Human Cancermentioning

confidence: 99%

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

Saloman

Bianco

Ebert

et al. 2000

Endocrine-Related Cancer

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The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/ posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-β (TGFβ)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in β-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of β-casein and whey acidic protein.In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

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“…CR-1 is overexpressed in a number of different types of human carcinomas and has been demonstrated to modulate the signaling of these pathways in human tumor cell lines in vitro (Adamson et al, 2002). In vivo, experiments have shown that tumor growth can be suppressed by downregulation of CR-1 using an antisense strategy Normanno et al, 1996Normanno et al, , 1999De Luca et al, 1997 or inhibition of CR-1's CFC signaling domain with an anti-CR-1 mouse monoclonal antibody or with an anti-EGF-like domain CR-1 rat monoclonal antibody Xing et al, 2004). These experiments validate that blockade of CR-1 can modulate tumor growth and points to CR-1 as a potential therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma

et al. 2005

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Human Cripto-1 (CR-1) is overexpressed in approximately 80% of human breast, colon and lung carcinomas. Mouse Cr-1 upregulation is also observed in a number of transgenic (Tg) mouse mammary tumors. To determine whether CR-1 can alter mammary gland development and/or may contribute to tumorigenesis in vivo, we have generated Tg mouse lines that express human CR-1 under the transcriptional control of the mouse mammary tumor virus (MMTV). Stable Tg MMTV/CR-1 FVB/N lines expressing different levels of CR-1 were analysed. Virgin female MMTV/CR-1 Tg mice exhibited enhanced ductal branching, dilated ducts, intraductal hyperplasia, hyperplastic alveolar nodules and condensation of the mammary stroma. Virgin aged MMTV/CR-1 Tg mice also possessed persistent end buds. In aged multiparous MMTV/ CR-1 mice, the hyperplastic phenotype was most pronounced with multifocal hyperplasias. In the highest CR-1-expressing subline, G4, 38% (12/31) of the multiparous animals aged 12-20 months developed hyperplasias and approximately 33% (11/31) developed papillary adenocarcinomas. The long latency period suggests that additional genetic alterations are required to facilitate mammary tumor formation in conjunction with CR-1. This is the first in vivo study that shows hyperplasia and tumor growth in CR-1-overexpressing animals.

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Synergistic growth inhibition and induction of apoptosis by a novel mixed backbone antisense oligonucleotide targeting CRIPTO in combination with C225 anti-EGFR monoclonal antibody and 8-Cl-cAMP in human GEO colon cancer cells.

Cited by 12 publications

References 0 publications

Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma

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