CD24 controls Src/STAT3 activity in human tumors

Bretz, Niko P.; Salnikov, Alexei V.; Perne, Claudia; Keller, Sascha; Wang, Xiaoli; Mierke, Claudia Tanja; Fogel, Mina; Erbe-Hofmann, Natalie; Schlange, Thomas; Moldenhauer, Gerhard; Altevogt, Peter

doi:10.1007/s00018-012-1055-9

Cited by 68 publications

(73 citation statements)

References 48 publications

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“…CD24 is reported to physically interact with c-src in both breast and ovarian cancer to regulate STAT3 (44–46). In hepatocellular carcinoma, CD24 has been shown to promote self-renewal through Nanog mediated by STAT3 phosphorylation (30).…”

Section: Discussionmentioning

confidence: 99%

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

Burgos-Ojeda

McLean

et al. 2015

Molecular Cancer Therapeutics

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Ovarian cancer is known to be composed of distinct populations of cancer cells, some of which demonstrate increased capacity for cancer initiation and/or metastasis. The study of human cancer cell populations is difficult due to long requirements for tumor growth, inter-patient variability and the need for tumor growth in immune-deficient mice. We therefore characterized the cancer initiation capacity of distinct cancer cell populations in a transgenic murine model of ovarian cancer. In this model, conditional deletion of Apc, Pten, and Trp53 in the ovarian surface epithelium (OSE) results in the generation of high grade metastatic ovarian carcinomas. Cell lines derived from these murine tumors express numerous putative stem cell markers including CD24, CD44, CD90, CD117, CD133 and ALDH. We show that CD24+ and CD133+ cells have increased tumor sphere forming capacity. CD133+ cells demonstrated a trend for increased tumor initiation while CD24+ cells vs CD24− cells, had significantly greater tumor initiation and tumor growth capacity. No preferential tumor initiating or growth capacity was observed for CD44+, CD90+, CD117+, or ALDH+ versus their negative counterparts. We have found that CD24+ cells, compared to CD24− cells, have increased phosphorylation of STAT3 and increased expression of STAT3 target Nanog and c-myc. JAK2 inhibition of STAT3 phosphorylation preferentially induced cytotoxicity in CD24+ cells. In vivo JAK2 inhibitor therapy dramatically reduced tumor metastases, and prolonged overall survival. These findings indicate that CD24+ cells play a role in tumor migration and metastasis and support JAK2 as a therapeutic target in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

Burgos-Ojeda

McLean

et al. 2015

Molecular Cancer Therapeutics

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“…65,[69][70][71] Targeting CD24 with antibody resulted in the significant reduction of immortalized lung tumor cells in a xenograft model. 72 Recent studies have reported significantly improved outcomes in B-lymphoid malignancies by use of antibody drug and chimeric-antigen receptor T cells (CART). 73,74 Development of new therapeutic agents targeting molecules identified in the present study using CART technology may prove beneficial to MLL-rearranged ALL, the majority which are infants.…”

Section: Discussionmentioning

confidence: 99%

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

Aoki

Watanabe

Saito

et al. 2015

Blood

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“…An impact on integrin-mediated cell binding was also noted in human carcinoma cell lines that overexpressed CD24 [24,25]. It was shown that CD24 triggers Src activity that in turn leads to the activation of FAK and STAT3 [29]. Independently, similar findings were reported for rat MTLy breast cancer cells carrying an doxocycline-inducible CD24 gene [34].…”

Section: Discussionmentioning

confidence: 70%

“…Samples were separated on SDS-PAGE gels and transferred to Immobilon membranes using semi-dry blotting. Western blot analysis was essentially as described before using biotinylated M1.69 followed by Streptavidin-Peroxidase [29]. Blots were reprobed with mAb to beta-actin as loading control.…”

Section: Cell Lysis and Western Blot Analysismentioning

confidence: 99%