Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

Angelis, E. de; Grassi, Michele; Gullick, William J.; Johnson, Gibbes R.; Rossi, G; Tempesta, Alfonso; Angelis, Francesco De; Luca, Antonella De; Salomon, David; Normanno, Nicola

doi:10.3892/ijo.14.3.437

Cited by 13 publications

(13 citation statements)

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“…In this regard, we found that CR-1 mRNA is expressed at low levels in normal human breast as compared with the levels of CR-1 mRNA in breast tumors. In contrast, a high frequency of CR-1 expression has been observed in colon tissue surrounding primary tumors and in the colon mucosa of individuals at high-risk, in whom CR-1 expression is associated with increased proliferation (36). The expression of CR-1 has also been observed in colon cancer premalignant lesions such as colon adenomas and in gastric metaplasia, suggesting that the expression of CR-1 may be a common event in human tumorigenesis (37,38).…”

Section: Discussionmentioning

confidence: 90%

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

Bianco

Strizzi

Mancino

et al. 2006

Clinical Cancer Research

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Purpose: Human Cripto-1 (CR-1), a cell membrane glycosylphosphatidylinositol-anchored glycoprotein that can also be cleaved from the membrane, is expressed at high levels in several different types of human tumors.We evaluated whether CR-1is present in the plasma of patients with breast and colon cancer, and if it can represent a new biomarker for these malignancies. Experimental Design: We determined CR-1 plasma levels using a sandwich-type ELISA in 21 healthy volunteers, 54 patients with breast cancer, 33 patients with colon carcinoma, and 21 patients with benign breast lesions. Immunohistochemical analysis was also used to assess CR-1expression in cancerous tissues. Results: Very low levels of CR-1 (mean F SD) were detected in the plasma of healthy volunteers (0.32 F 0.19 ng/mL). A statistically significant increase in the levels of plasma CR-1was found in patients with colon carcinoma (4.68 F 3.5 ng/mL) and in patients with breast carcinoma (2.97 F 1.48 ng/mL; P < 0.001). Although moderate levels of plasma CR-1 were found in women with benign lesions of the breast (1.7 F 0.99 ng/mL), these levels were significantly lower than in patients with breast cancer (P < 0.001). Finally, immunohistochemical analysis and real-time reverse transcription-PCR confirmed strong positivity for CR-1 in colon and/or breast tumor tissues. Conclusion: This study suggests that plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas.

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Section: Discussionmentioning

confidence: 90%

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

Bianco

Strizzi

Mancino

et al. 2006

Clinical Cancer Research

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“…This hypothesis is in agreement with recent in vitro findings discussed above that have demonstrated that expression of CR-1 is associated with increased motility and invasiveness of tumor cells Bianco et al, 2003;Normanno et al, 2004;Strizzi et al, 2004). Interestingly, CR-1 is frequently coexpressed with other EGF-related peptides, such as TGF-b, amphiregulin and heregulin in human breast and mouse epidermal carcinomas, implying that different growth factors might cooperate in supporting the autonomous proliferation of cancer cells (Saeki et al, 1992;Qi et al, 1994;Normanno et al, 1995;Panico et al, 1996;De Angelis et al, 1999;D'Antonio et al, 2002;Liu et al, 2003). Finally, expression of CR-1 has been reported in other carcinoma types, including lung carcinoma (Fontanini et al, 1998), nonseminomatous testicular tumors (Baldassarre et al, 1997), pancreatic ductal adenocarcinoma (Friess et al, 1994;Tsutsumi et al, 1994), basal cell carcinoma (Welss et al, 2003) and bladder carcinoma (Byrne et al, 1998).…”

Section: In Vivo Tumorigenesis Induced By Cripto-1mentioning

confidence: 90%

“…In this respect, the frequency of CR-1 expression in the adenomas was found to correlate directly with the degree of dysplasia, and with the size and the histological subtype of colon adenomas (Saeki et al, 1994b). CR-1 expression was also detected in 62% of normal colon mucosa specimens from individuals that belong to families with a high incidence of colorectal carcinomas, whereas only 20% of colon mucosa from low-risk patient specimens was positive for CR-1 (De Angelis et al, 1999). In an additional study, expression of CR-1 immunoreactivity in normal rectal mucosa adjacent to carcinoma was associated with an increase in the incidence of bowel wall penetration, lymph node involvement and a recurrence rate of 100% (Gagliardi et al, 1994).…”

Section: In Vivo Tumorigenesis Induced By Cripto-1mentioning

confidence: 93%

“…Expression of CR-1 mRNA and/or immunoreactive protein has been demonstrated to occur with high frequency in colorectal, breast, ovarian and gastric cancers in different studies that have examined a relevant number of tumor specimens (Kuniyasu et al, 1991;Saeki et al, 1992Saeki et al, , 1994aQi et al, 1994;Stromberg et al, 1994;Normanno et al, 1995;Panico et al, 1996;Niikura et al, 1997;De Angelis et al, 1999;D'Antonio et al, 2002). Expression of CR-1 in normal tissues has been examined in some of these studies.…”

Section: In Vivo Tumorigenesis Induced By Cripto-1mentioning

confidence: 99%

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Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

et al. 2005

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It is increasingly evident that genes known to perform critical roles during early embryogenesis, particularly during stem cell renewal, pluripotentiality and survival, are also expressed during the development of cancer. In this regard, oncogenesis may be considered as the recapitulation of embryogenesis in an inappropriate temporal and spatial manner. The epidermal growth factor-Cripto-1/FRL1/cryptic family of proteins consists of extracellular and cell-associated proteins that have been identified in several vertebrate species. During early embryogenesis, epidermal growth factor-Cripto-1/FRL1/ cryptic proteins perform an obligatory role as coreceptors for the transforming growth factor-beta subfamily of proteins, which includes Nodal. Cripto-1 has also been shown to function as a ligand through a Nodal/Alk4-independent signaling pathway that involves binding to glypican-1 and the subsequent activation through src of phosphoinositol-3 kinase/Akt and ras/mitogen-activated protein kinase intracellular pathways. Expression of Cripto-1 is increased in several human cancers and its overexpression is associated with the development of mammary tumors in mice. Here, we review the role of Cripto-1 during embryogenesis, cell migration, invasion and angiogenesis and how these activities may relate to cellular transformation and tumorigenesis. We also briefly discuss evidence suggesting that Cripto-1 may be involved in stem cell maintenance.

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“…While Cripto-1 is usually expressed at low levels in normal adult tissues, a significant increase in Cripto-1 expression has been shown in premalignant lesions of the colon, stomach and breast [39–42]. Cripto-1 expression has also been detected in patients with long-term Helicobacter pylori infection and athrophic gastritis, two risk factors for gastric carcinogenesis, and in the normal colon mucosa from individuals that belong to families with high risk of colorectal carcinomas [43, 44]. Recently, high levels of Cripto-1 expression in colorectal tumors have been found to be associated with metachronous metastasis and poor prognosis [45].…”

Section: Cripto-1 Expression In Human Tumorsmentioning

confidence: 99%

Targeting the embryonic gene Cripto-1 in cancer and beyond

Bianco

Salomon

2010

Expert Opinion on Therapeutic Patents

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Importance of the field-Emerging evidence has clearly implicated an inappropriate activation of embryonic regulatory genes during cell transformation in adult tissues. An example of such a case is the embryonic gene Cripto-1. Cripto-1 is critical for embryonic development and is considered a marker of undifferentiated embryonic stem cells. Critpo-1 is expressed at low levels in adult tissues, but is re-expressed at a high frequency in a number of different types of human carcinomas, therefore representing an attractive therapeutic target in cancer.Area covered in this review-This review surveys different approaches that have been used to target Cripto-1 in cancer as reflected by the relevant patent literature as well as peer-reviewed publications. Potential involvement and targeting of Cripto-1 in neurodegenerative and degenerative muscle diseases are also discussed.What the reader will gain-The reader will gain an overview of different monoclonal antibodies, vaccines or oligonucleotides antisense targeting Cripto-1. A humanized anti-Cripto-1 antibody is currently being tested in a phase I clinical trial in cancer patients.Take home message-Targeting Cripto-1 in human tumors has the potential to eliminate not only differentiated cancer cells but also destroy an undifferentiated subpopulation of cancer cells with stem-like characteristics that support tumor initiation and self-renewal.

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Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

Cited by 13 publications

References 0 publications

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

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

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

Targeting the embryonic gene Cripto-1 in cancer and beyond

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