Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

Henry, Claire; Llamosas, Estelle; Knipprath-Mészáros, Alexandra Maria; Schoetzau, Andreas; Obermann, Ellen C.; Fuenfschilling, Maya; Caduff, R.; Fink, Daniel; Hacker, Neville F.; Ward, Robyn L.; Heinzelmann‐Schwarz, Viola; Ford, Caroline

doi:10.18632/oncotarget.5643

Cited by 62 publications

(98 citation statements)

References 32 publications

(45 reference statements)

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“…In contrast, studies involving a large number of patients found that upregulation of Wnt5a was associated with a relatively poor prognosis [54–58]. Compared with the frequency of Wnt1 expression in ovarian cancer, Wnt5a was more frequently found in malignant epithelial ovarian cancer patients (80% out of a total 38) [54].…”

Section: Wnt5a Signaling In Ovarian Cancer Stem Cellsmentioning

confidence: 99%

Wnt5a Signaling in Normal and Cancer Stem Cells

Zhou

Kipps

Zhang

2017

Stem Cells International

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Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

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Section: Wnt5a Signaling In Ovarian Cancer Stem Cellsmentioning

confidence: 99%

Wnt5a Signaling in Normal and Cancer Stem Cells

Zhou

Kipps

Zhang

2017

Stem Cells International

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“…It is recognized that ROR1 and ROR2 expression diminishes in adult tissue [27], with many studies indicating increased expression associated with malignant progression [3], [4], [10], [11], [12], [28], [29], [30]. We have previously found ROR2 and its receptor, WNT5A, to be upregulated in OC [13], [31], [32] patient samples and have shown in vitro that both ROR1 and ROR2 are important in OC migration and invasion, indicating a role in OC metastasis [32]. However, it is unknown how the receptors interplay, and therefore, we aimed to analyze the expression of both receptors in the same cohort.…”

Section: Resultsmentioning

confidence: 95%

“…In many cases, the receptor tyrosine kinases ROR1 and ROR2 are abnormally overexpressed in tumors and associated with stem cell properties, epithelial to mesenchymal transition, and metastasis [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. In OC, we have previously shown that both ROR1 and ROR2 are important in cell growth, migration, and invasion [13]. Others have confirmed the role of ROR1 in OC and have found that inhibiting ROR1 using a monoclonal antibody halts the growth of tumor xenografts [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

Henry

Emmanuel

Lambie

et al. 2017

Translational Oncology

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OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

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“…Yes (127) Yes (128) Breast cancer (86,87) ; melanoma (92,94) ; non-small cell lung cancer (129) ; gastric cancer (130) ; ovarian cancer (131) …”

Section: Ror1mentioning

confidence: 99%

“…Yes (19,127,132) Yes (48,133) Breast cancer (81) ; prostate cancer (41) ; melanoma (90,92) ; non-small cell lung cancer (134) ; colorectal cancer (135) ; gastric cancer (136) ; ovarian cancer (131) …”

Section: Ror2mentioning

confidence: 99%

WNT5A and Its Receptors in the Bone-Cancer Dialogue

Thiele

Rachner

Rauner

et al. 2016

Journal of Bone and Mineral Research

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Wnt signaling is critical for tumorigenesis and skeletal remodeling. However, its contribution to the formation of metastatic bone lesions remains poorly defined. One major challenge of unraveling its role in cancer progression is the high complexity of Wnt signaling, which includes numerous ligands, receptors, and inhibitors, with intricate biological effects and specific signaling pathways depending on the cellular context. In this perspective, we summarize the role of the noncanonical Wnt ligand WNT5A in the development and metastatic process of osteotropic cancer entities. We focus on its tumor-suppressive function in breast cancer, tumor promoting effects in melanoma, and ambiguous role in prostate cancer, and discuss potential challenges and opportunities that may be associated with targeting Wnt signaling for cancer therapy and treatment of bone metastases.

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Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

Cited by 62 publications

References 32 publications

Wnt5a Signaling in Normal and Cancer Stem Cells

Wnt5a Signaling in Normal and Cancer Stem Cells

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

WNT5A and Its Receptors in the Bone-Cancer Dialogue

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