ALDH1-Bright Epithelial Ovarian Cancer Cells Are Associated with CD44 Expression, Drug Resistance, and Poor Clinical Outcome

Wang, Yu Chi; Yo, Yi Te; Lee, Hsin Yi; Liao, Yu Ping; Chao, Tai-Kuang; Su, Po Hsuan; Lai, Hung Cheng

doi:10.1016/j.ajpath.2011.11.015

Cited by 150 publications

(147 citation statements)

References 43 publications

(63 reference statements)

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“…S2E). Consistent with previous reports (17,22), the cells within such spheroids were enriched for cells that had high levels of ALDH1 expression (Fig. S2F).…”

Section: Resultssupporting

confidence: 79%

“…Compared with ROR1 Low cases, ROR1 Hi ovarian cancers had higher expression of gene signatures associated with the side population, which may contain CSCs (42). Moreover, ROR1 Hi ovarian cancers were enriched for expression of genes associated with embryonic stem cells and EMT (17,25), which facilitates the capacity of tumor cells to migrate and seed metastatic sites (21,43). We also observed that two primary ovarian cancers that expressed ROR1 were better able to grow as xenografts in immune-deficient mice than one that lacked expression of ROR1.…”

Section: Discussionmentioning

confidence: 93%

“…Ovarian CSCs also can extrude small molecules, such as various chemotherapeutic drugs or fluorescent dyes, allowing for their identification as a less fluorescent "side population" in flowcytometric analysis of tumor cells stained with the DNA-binding dye Hoechst 33342 (14)(15)(16). Furthermore, ovarian CSCs may express various surface antigens, such as CD44, CD117, or CD133 (7,8,(17)(18)(19). Functionally, human ovarian CSCs apparently can form nonadherent cellular spheres, called "spheroids," which in turn are enriched for ovarian cancer cells that have high ALDH1 activity, are relatively resistant to chemotherapeutic drugs, and have enhanced potential for seeding metastatic sites or engrafting immune-deficient mice (5,17,18,(20)(21)(22).…”

mentioning

confidence: 99%

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Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Zhang

Cui

Lai

et al. 2014

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

161

156

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Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1 + ) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1 Neg ) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1 + cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.ROR1 | ovarian cancer stem cell | monoclonal antibody | PDX mice model

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“…S2E). Consistent with previous reports (17,22), the cells within such spheroids were enriched for cells that had high levels of ALDH1 expression (Fig. S2F).…”

Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

See 1 more Smart Citation

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Zhang

Cui

Lai

et al. 2014

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

161

156

View full text Add to dashboard Cite

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“…Previous studies showed successful isolation of ovarian CSCs/CICs by the ALDEFLUOR assay. 22 Therefore, the ALDEFLUOR assay is a promising approach to isolate ovarian CSCs/CICs. We next examined the action of fibroblasts on the tumor initiation capacity of CSCs/CICs and the histology of tumors.…”

Section: Discussionmentioning

confidence: 99%

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Yasuda

Torigoe

Mariya

et al. 2014

Laboratory Investigation

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Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tumorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/ CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1 high ) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1 high cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1 high cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1 high cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1 high cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as stemness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1 high cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1 high cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

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“…aureus is a pathogenic bacterium that is the cause of numerous infections (15). As one of the most important pathogens in orthopaedic infections (16), the treatment of S. aureus is of the utmost importance.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial effects of bacteriocins isolated from Lactobacillus rhamnosus (ATCC 53103) in a rabbit model of knee implant infection

Zhou

Zhang

2018

Exp Ther Med

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Abstract. Infection following orthopedic surgery is a major complication that can have serious implications on patient health. The present study aimed to investigate the antibacterial effects of bacteriocins obtained from Lactobacillus rhamnosus on a rabbit model of Staphylococcus aureus infection following knee replacement surgery. Blood samples were collected 1, 2, 3, 4 and 5 days after bacteriocin injection, and C-reactive protein (CRP) and interleukin (IL)-6 levels were measured using commercial ELISA kits. In addition, biofilm formation was evaluated by fluorescence microscopy. Bacteriocins were identified to exhibit significant inhibitory effects on Staphylococcus aureus biofilm formation, and on CRP and IL-6 levels in the serum, following surgery and infection (all P<0.05 vs. the control group). The results of the present study indicate that bacteriocins are a potential agent for the prevention of orthopedic postoperative infections.

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ALDH1-Bright Epithelial Ovarian Cancer Cells Are Associated with CD44 Expression, Drug Resistance, and Poor Clinical Outcome

Cited by 150 publications

References 43 publications

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Antibacterial effects of bacteriocins isolated from Lactobacillus rhamnosus (ATCC 53103) in a rabbit model of knee implant infection

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