Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer

Bianco, Caterina; Strizzi, Luigi; Mancino, Mario; Rehman, Aasia O.; Hamada, Shin; Watanabe, Kazuhide; Luca, Antonella De; Jones, Brenda; Balogh, Gabriela Andrea; Russo, José; Mailo, Daniel; Palaia, Raffaéle; D’Aiuto, Giuseppe; Botti, Gerardo; Perrone, Francesco; Salomon, David; Normanno, Nicola

doi:10.1158/1078-0432.ccr-06-0274

Cited by 80 publications

(88 citation statements)

References 36 publications

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“…This study further demonstrated that Cripto, a prominent mediator of the Nodal signaling pathway in embryological systems, also is restricted to multipotent cancer and stem cell fates. Previous studies, from other laboratories, determined that like Nodal, Cripto is expressed in cancer, specifically testicular, colon and breast cancer cells, but is rarely detected in normal adult tissues (22)(23)(24). Furthermore, Cripto is a stem cell marker for pluripotent hESCs and has been associated with dedifferentiation, vascularization and invasion in breast carcinoma cells (23,25,26).…”

Section: Discussionmentioning

confidence: 99%

Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells

Postovit

Margaryan

Seftor

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

268

332

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Embryonic stem cells sustain a microenvironment that facilitates a balance of self-renewal and differentiation. Aggressive cancer cells, expressing a multipotent, embryonic cell-like phenotype, engage in a dynamic reciprocity with a microenvironment that promotes plasticity and tumorigenicity. However, the cancerassociated milieu lacks the appropriate regulatory mechanisms to maintain a normal cellular phenotype. Previous work from our laboratory reported that aggressive melanoma and breast carcinoma express the embryonic morphogen Nodal, which is essential for human embryonic stem cell (hESC) pluripotency. Based on the aberrant expression of this embryonic plasticity gene by tumor cells, this current study tested whether these cells could respond to regulatory cues controlling the Nodal signaling pathway, which might be sequestered within the microenvironment of hESCs, resulting in the suppression of the tumorigenic phenotype. Specifically, we discovered that metastatic tumor cells do not express the inhibitor to Nodal, Lefty, allowing them to overexpress this embryonic morphogen in an unregulated manner. However, exposure of the tumor cells to a hESC microenvironment (containing Lefty) leads to a dramatic down-regulation in their Nodal expression concomitant with a reduction in clonogenicity and tumorigenesis accompanied by an increase in apoptosis. Furthermore, this ability to suppress the tumorigenic phenotype is directly associated with the secretion of Lefty, exclusive to hESCs, because it is not detected in other stem cell types, normal cell types, or trophoblasts. The tumor-suppressive effects of the hESC microenvironment, by neutralizing the expression of Nodal in aggressive tumor cells, provide previously unexplored therapeutic modalities for cancer treatment.Lefty ͉ Nodal ͉ melanoma ͉ breast carcinoma

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Section: Discussionmentioning

confidence: 99%

Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells

Postovit

Margaryan

Seftor

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

268

332

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“…5A). In addition, significantly higher levels of Cripto-1 can be detected by immunoassay in the plasma of breast cancer patients as compared to Cripto-1 levels detected in healthy controls suggesting that Cripto-1 might be useful in the early diagnosis of this disease [94] (Fig. 5A).…”

Section: Diagnostic and Therapeutic Applicationmentioning

confidence: 98%

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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“…19 Additionally, both forms of cancer have an increased expression of FAK and CR-1. 20,21 In addition to expressing similar biomarkers, morphologically both MCF-7 (Ref. 22) and HCT 116 (Ref.…”

Section: Introductionmentioning

confidence: 99%

Separation of tumor cells with dielectrophoresis-based microfluidic chip

et al. 2013

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The present work demonstrates the use of a dielectrophoretic lab-on-a-chip device in effectively separating different cancer cells of epithelial origin for application in circulating tumor cell (CTC) identification. This study uses dielectrophoresis (DEP) to distinguish and separate MCF-7 human breast cancer cells from HCT-116 colorectal cancer cells. The DEP responses for each cell type were measured against AC electrical frequency changes in solutions of varying conductivities. Increasing the conductivity of the suspension directly correlated with an increasing frequency value for the first cross-over (no DEP force) point in the DEP spectra. Differences in the cross-over frequency for each cell type were leveraged to determine a frequency at which the two types of cell could be separated through DEP forces. Under a particular medium conductivity, different types of cells could have different DEP behaviors in a very narrow AC frequency band, demonstrating a high specificity of DEP. Using a microfluidic DEP sorter with optically transparent electrodes, MCF-7 and HCT-116 cells were successfully separated from each other under a 3.2 MHz frequency in a 0.1X PBS solution. Further experiments were conducted to characterize the separation efficiency (enrichment factor) by changing experimental parameters (AC frequency, voltage, and flow rate). This work has shown the high specificity of the described DEP cell sorter for distinguishing cells with similar characteristics for potential diagnostic applications through CTC enrichment. V C 2013 American Institute of Physics. [http://dx

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Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer

Cited by 80 publications

References 36 publications

Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells

Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells

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

Separation of tumor cells with dielectrophoresis-based microfluidic chip

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