Ductal Carcinoma In Situ Progression in Dog Model of Breast Cancer

Mohammed, Sulma I.; Utturkar, Sagar M.; Lee, Maxwell; Yang, Howard; Cui, Zelin; Atallah, Nadia M.; Zhang, Guangjun; Cardona, Xavier E Ramos; Mittal, Suresh K.; Miller, Margaret A.

doi:10.3390/cancers12020418

Cited by 18 publications

(20 citation statements)

References 51 publications

(72 reference statements)

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“…So, in the context of breast cancer, SFRP2 levels in serum may be a promising biomarker and prognostic prediction tool. The relationship between SFRP2 expression and poor survival in breast cancer was further confirmed by Hill et al [72] and Mohammed et al [73]. A similar correlation between protein expression and prognosis was observed in osteosarcoma [74] and CRC patients [75].…”

Section: Sfrp2 As a Tumor Promotorsupporting

confidence: 52%

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

Loon

Huijbers

2020

Cancer Metastasis Rev

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Secreted frizzled-related proteins (SFRP) are glycoproteins containing a so-called frizzled-like cysteine-rich domain. This domain enables them to bind to Wnt ligands or frizzled (FzD) receptors, making potent regulators of Wnt signaling. As Wnt signaling is often altered in cancer, it is not surprising that Wnt regulators such as SFRP proteins are often differentially expressed in the tumor microenvironment, both in a metastatic and non-metastatic setting. Indeed, SFRP2 is shown to be specifically upregulated in the tumor vasculature of several types of cancer. Several studies investigated the functional role of SFRP2 in the tumor vasculature, showing that SFRP2 binds to FzD receptors on the surface of tumor endothelial cells. This activates downstream Wnt signaling and which is, thereby, stimulating angiogenesis. Interestingly, not the well-known canonical Wnt signaling pathway, but the noncanonical Wnt/Ca2+ pathway seems to be a key player in this event. In tumor models, the pro-angiogenic effect of SFRP2 could be counteracted by antibodies targeting SFRP2, without the occurrence of toxicity. Since tumor angiogenesis is an important process in tumorigenesis and metastasis formation, specific tumor endothelial markers such as SFRP2 show great promise as targets for anti-cancer therapies. This review discusses the role of SFRP2 in noncanonical Wnt signaling and tumor angiogenesis, and highlights its potential as anti-angiogenic therapeutic target in cancer.

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Section: Sfrp2 As a Tumor Promotorsupporting

confidence: 52%

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

Loon

Huijbers

2020

Cancer Metastasis Rev

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“…25 Recently, transcriptomic studies along the continuum of cancer progression in the canine mammary gland, from healthy to early malignant and finally invasive carcinoma, were described and compared to the situation in humans, further supporting this observation. 26 We hypothesised that neuter status also had an influence on the before mentioned histological continuum. The first objective of this study was to compare a population of MT bearing dogs to a large control population of bitches without MTs.…”

mentioning

confidence: 99%

Ovariectomy reduces the risk of tumour development and influences the histologic continuum in canine mammary tumours

Gedon¹,

Wehrend

Kessler³

2021

Vet Comparative Oncology

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Influence of neutering on canine mammary tumorigenesis has been a source of vivid discussion over the last decades. The purpose of this retrospective study was to describe the association between neuter status, tumour size and degree of malignancy in a large population of 625 female dogs with altogether 1459 removed mammary tumours (MTs). MT‐bearing dogs were predominantly intact (80.3%) and intact dogs were overrepresented in the tumour population compared to the control group of >19 000 females (p < .0001). Multiple MT occurred in 340 patients (54.4%) and were significantly more common in intact dogs (57.8% vs. 40.7% spayed). Neutered dogs were not only significantly more likely to have a malignant MT (p < .0001) but were significantly more often affected by more aggressive tumour subtypes (p < .0001). Positive correlation between increasing tumour size and increasingly malignant phenotype was slightly stronger in spayed (rs = .217; p = .021) compared to intact (rs = .179; p = .0003) patients. After ovariectomy, progression from benign to malignant occurs in smaller size tumours, as MT ≥2 cm in diameter were malignant in 86.9% of the spayed patients, compared to 62.0% in intact patients (p = .0002). Intact bitches have a higher risk for MTs and tumour multiplicity. MTs in neutered females are more often malignant and belong to more aggressive subtypes compared to MTs in intact dogs. In neutered bitches, histologic progression from benign to malignant and further along the cancer progression continuum occurs at smaller tumour sizes.

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“…In renal cancer, enforced SFRP2 expression facilitates proliferation and in vivo tumor growth of renal cancer cells by activating canonical Wnt signaling [ 24 ]. In addition, SFRP2 is also upregulated and associated with poor prognosis of breast cancer and colorectal cancer [ 25 , 26 ]. On the contrary, SFRP2 is demonstrated to act as tumor suppressor in many other cancers, too.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling

Yin

Zhao

et al. 2021

PLoS ONE

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Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/β-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/β-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/β-catenin activation. Besides, pharmacological inhibition of Wnt/β-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/β-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients.

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Ductal Carcinoma In Situ Progression in Dog Model of Breast Cancer

Cited by 18 publications

References 51 publications

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis

Ovariectomy reduces the risk of tumour development and influences the histologic continuum in canine mammary tumours

Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling

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