ROR1 expression correlated with poor clinical outcome in human ovarian cancer

Zhang, Huilin; Qiu, Jiliang; Ye, Chunping; Yang, Dan; Gao, Liyuan; Su, Yiping; Tang, Xiaojun; Xu, Ning; Zhang, Dawei; Xiong, Lin; Yuan, Man; Li, Fengshan; Zhu, Jin

doi:10.1038/srep05811

Cited by 88 publications

(79 citation statements)

References 36 publications

(51 reference statements)

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“…Consistent with these observations, we noted that ovarian cancers that expressed ROR1 by immunohistochemistry more commonly had a high-grade, less-differentiated histology (30), which typically is associated with aggressive disease (41). This also is consistent with a recently published study indicating that high-level expression of ROR1, assessed by immunohistochemistry of primary tumor tissue, was an independent prognostic factor for predicting relatively short diseasefree survival or overall survival of patients with ovarian cancer (34). We found ovarian cancers that expressed high levels of ROR1 had gene-expression signatures associated with CSCs.…”

Section: Discussionsupporting

confidence: 91%

“…Conversely, silencing ROR1 in metastasis-prone breast-cancer cell lines could attenuate expression of genes associated with EMT and impair their migration/invasion capacity in vitro and their metastatic potential in vivo (33). Very recently, Zhang et al reported that high-level expression of ROR1 was an independent prognostic factor for predicting relatively short disease-free survival or overall survival of patients with ovarian cancer (34). In this study, we examined whether ovarian cancer cells that Significance This study demonstrates that the oncoembryonic surface antigen, receptor tyrosine kinase-like orphan receptor 1 (ROR1), is expressed on human ovarian cancer stem cells (CSCs), on which it seems to play a functional role in promoting migration/invasion or spheroid formation in vitro and tumor engraftment in immune-deficient mice.…”

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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.

158

145

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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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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

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.

158

145

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“…A variety of different cancers have been found to express ROR1. 23 To date, high-level expression of ROR1 has been found to have adverse prognostic significance for patients with breast cancer, [24][25][26][27] ovarian cancer, 28,29 melanoma, 30 or Ewing sarcoma. 31 Moreover, high-level expression of ROR1 also has been associated with higher levels of AKT activation, 24,30,32,33 consistent with the notion that ROR1 signaling leading to activation of AKT may serve as a driver, not just in CLL, but also in other malignancies.…”

Section: Discussionmentioning

confidence: 99%

High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia

Cui

Ghia

Chen

et al. 2016

Blood

106

120

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which we randomly assigned to a training or validation set of 797 or 771 cases, respectively. Using recursive partitioning, we defined a threshold for ROR1 surface expression that could segregate samples of the training set into ROR1-Hi vs ROR1-Lo subgroups that differed significantly in their median treatment-free survival (TFS). Using this threshold, we found that ROR1-Hi cases had a significantly shorter median TFS and overall survival than ROR1-Lo cases in the validation set. These data demonstrate that expression of ROR1 may promote leukemia-cell activation and survival and enhance disease progression in patients with CLL. (Blood. 2016;128(25):2931-2940

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“…Some of these studies reported that ROR1 expression in breast and ovarian cancers is related to the higher tumor grade and aggressive behaviors [10,17]. However, another study reports that there is no different expression of ROR1 in progressive disease and nonprogressive disease of chronic lymphocytic leukemia [18].…”

Section: Discussionmentioning

confidence: 99%