CD24 Is a New Oncogene, Early at the Multistep Process of Colorectal Cancer Carcinogenesis

Sagiv, Eyal; Memeo, Lorenzo; Karin, Adi; Kazanov, Diana; Jacob-Hirsch, Jasmin; Mansukhani, Mahesh; Rechavi, Gidi; Hibshoosh, Hanina; Arber, Nadir

doi:10.1053/j.gastro.2006.04.028

Cited by 100 publications

(101 citation statements)

References 32 publications

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“…Discussion CD24 is a cell-surface protein that functions as a mediator of proliferation, invasion, and motility in multiple types of cancer cell lines from multiple tissues (4,11,12,30,31). Previous efforts to investigate the role of CD24 in the primary tumor setting have been limited to using exogenous overexpression and suppression in xenograft models.…”

Section: Ar Activation Stimulates Cd24 Promoter Activity In Human Blamentioning

confidence: 99%

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

Overdevest

Knubel²,

Duex³

et al. 2012

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

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Overexpression of CD24, a glycosyl phosphatidylinositol-linked sialoglycoprotein, is associated with poor outcome in urothelial carcinoma and contributes to experimental tumor growth and metastasis. However, the requirement for CD24 ( Cd24a in mice) in tumorigenesis and spontaneous metastasis from the orthotopic site remains uncharacterized. Using N -butyl- N -(4-hydroxybutyl) nitrosamine induction of invasive and metastatic bladder cancer, we show that Cd24a -deficient male mice developed fewer bladder tumors than C57BL/6 control male mice. Evaluating only mice with evidence of primary tumors, we observed that Cd24a- deficient male mice also had fewer metastases than wild-type counterparts. In parallel observations, stratification of patients based on CD24 immunohistochemical expression in their tumors revealed that high levels of CD24 are associated with poor prognosis in males. In female patients and mice the above observations were not present. Given the significant role of CD24 in males, we sought to assess the relationship between androgen and CD24 regulation. We discovered that androgen receptor knockdown in UM-UC-3 and TCCSUP human urothelial carcinoma cell lines resulted in suppression of CD24 expression and cell proliferation. Androgen treatment also led to increased CD24 promoter activity, dependent on the presence of androgen receptor. In vivo, androgen deprivation resulted in reduced growth and CD24 expression of UM-UC-3 xenografts, and the latter was rescued by exogenous CD24 overexpression. These findings demonstrate an important role for CD24 in urothelial tumorigenesis and metastasis in male mice and indicate that CD24 is androgen regulated, providing the foundation for urothelial bladder cancer therapy with antiandrogens.

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Section: Ar Activation Stimulates Cd24 Promoter Activity In Human Blamentioning

confidence: 99%

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

Overdevest

Knubel²,

Duex³

et al. 2012

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

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“…20,21,24,39 Interestingly, it has only recently been suggested as a cancer stem cell marker in the gastrointestinal tract and in the liver. 40,41 The only known ligand for CD24 is P-selectin which mediates binding to platelets and endothelial cells and therefore could enhance the formation of tumor thrombi and metastases.…”

Section: Immunophenotyping Of Ampullary Tumors D Baumhoer Et Almentioning

confidence: 99%

“…[19][20][21][22][23][24] Also intraand extrahepatic cholangiocarcinomas have been reported to express CD24. [25][26][27] P-cadherin was found to be constantly upregulated in intrahepatic cholangiocarcinomas using cDNA microarray technique that was confirmed using immunohistochemistry.…”

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confidence: 99%

Expression of CD24, P-cadherin and S100A4 in tumors of the ampulla of Vater

et al. 2009

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Carcinomas of the Vaterian system are rare and presumably arise from preexisting adenomas (adenomacarcinoma-sequence). Usually, biopsies are obtained to confirm and specify endoscopic findings, but differentiating reactive atypia from dysplasia or dysplasia from invasive carcinoma can sometimes be difficult or even impossible on morphological criteria alone. In case of invasive carcinoma, furthermore, the precise classification of carcinoma subtypes needs to be established since the distinct subtypes differ significantly in terms of clinical outcome. The cell adhesion proteins CD24, P-cadherin and S100A4 were shown to be expressed in several carcinomas and in dysplastic epithelium but only rarely in normal mucosa. We therefore investigated their expression in 177 carcinoma, 114 adenoma and 152 normal mucosa specimens of the ampulla of Vater. Although the expression of the cell adhesion proteins did not differ between the carcinoma subtypes, marked differences between normal mucosa, adenoma and carcinoma samples were observed. All marker proteins were expressed in less than 7% of normal mucosa samples (S100A4 in only 1% of cases) and showed an increasing expression from adenoma to invasive carcinoma. Our findings suggest that P-cadherin and S100A4 are helpful in discriminating normal mucosa or reactive atypia from neoplastic lesions. CD24 and S100A4, furthermore, can assist in the differential diagnosis of dysplasia vs invasive carcinoma.

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“…In our previous studies, we had shown the importance of CD24 in the multistep process of colorectal cancer carcinogenesis, already at the early stage of adenoma (10). Stringently controlled conditional expression systems are crucial for the functional characterization of genes.…”

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confidence: 99%

The CD24 Protein Inducible Expression System Is an Ideal Tool to Explore the Potential of CD24 as an Oncogene and a Target for Immunotherapy in Vitro and in Vivo

Shapira

Kazanov²,

Weisblatt

et al. 2011

Journal of Biological Chemistry

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Background: It is critical to tightly regulate gene expression to study its biological role. Results: A tetracycline-dependent CD24 expression system was successfully implemented. An efficient study of its potential as an oncogene and a target for immunotherapy was performed. Conclusion: This is a valuable tool to study CD24 pathogenesis and novel treatment options for CD24-expressing malignancies. Significance: The CD24 inducible expression system allows accurate analysis of its role and function.

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CD24 Is a New Oncogene, Early at the Multistep Process of Colorectal Cancer Carcinogenesis

Cited by 100 publications

References 32 publications

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

CD24 expression is important in male urothelial tumorigenesis and metastasis in mice and is androgen regulated

Expression of CD24, P-cadherin and S100A4 in tumors of the ampulla of Vater

The CD24 Protein Inducible Expression System Is an Ideal Tool to Explore the Potential of CD24 as an Oncogene and a Target for Immunotherapy in Vitro and in Vivo

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