Quantitative analysis of HER2 mRNA expression by RNA in situ hybridization in canine mammary gland tumors: Comparison with immunohistochemistry analysis

Seung, Byung-Joon; Cho, Seung-Hee; Kim, S.-H.; Lim, Hyungjun; Sur, Jung-Hyang

doi:10.1371/journal.pone.0229031

Cited by 22 publications

(14 citation statements)

References 43 publications

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“…CK5/6 and EGFR help in the identification of basaltype tumors with aggressive behavior (48). The establishment of HER2-overexpressing tumors in dogs is challenging because HER2 overexpression is generally associated with the absence of HER2 genomic amplification (49,50). HER2 alterations in normal mammary cells were demonstrated previously using chromogenic in situ hybridization (CISH) (50).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines With Vasculogenic Mimicry Ability in vitro and in vivo

et al. 2020

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Mammary tumors affect intact and elderly female dogs, and almost 50% of these cases are malignant. Cell culture offers a promising preclinical model to study this disease and creates the opportunity to deposit cell lines at a cell bank to allow greater assay reproducibility and more reliable validation of the results. Another important aspect is the possibility of establishing models and improving our understanding of tumor characteristics, such as vasculogenic mimicry. Because of the importance of cancer cell lines in preclinical models, the present study established and characterized primary cell lines from canine mammary gland tumors. Cell cultures were evaluated for morphology, phenotype, vasculogenic mimicry (VM), and tumorigenicity abilities. We collected 17 primary mammary carcinoma and three metastases and obtained satisfactory results from 10 samples. The cells were transplanted to a xenograft model. All cell lines exhibited a spindle-shaped or polygonal morphology and expressed concomitant pancytokeratin and cytokeratin 8/18. Four cell lines had vasculogenic mimicry ability in vitro, and two cell lines showed in vivo tumorigenicity and VM in the xenotransplanted tumor. Cellular characterization will help create a database to increase our knowledge of mammary carcinomas in dogs, including studies of tumor behavior and the identification of new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines With Vasculogenic Mimicry Ability in vitro and in vivo

et al. 2020

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“…Previous studies identified HER-2 in normal, hyperplastic, and dysplastic mammary tissues and found no relation with prognostic parameters such as disease-free interval (DFI), overall survival (OS), and lymphovascular invasion, suggesting that HER-2 may play a role in the proliferation of mammary tissue in female dogs, but not conclusively in its malignant transformation ( 40 ). Furthermore, in a recent publication ( 44 ), HER-2 messenger RNA (mRNA) expression was observed in neoplastic and non-neoplastic mammary tissues using a novel quantitative RNA in situ hybridization assay, which correlates with the immunohistochemistry score. Among the non-neoplastic mammary tissues (hyperplasia), all cases showed HER-2: 21.4% were classified as 1+, while 78.6% were positive (2+ and 3+) ( Figure 6 ).…”

Section: Conventional and New Clinical And Histological Approachesmentioning

confidence: 98%

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

et al. 2021

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Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs. Canine mammary cancer (CMC) represents 50% of CMTs, and besides surgery, which is the elective treatment, additional targeted and non-targeted therapies could offer benefits in terms of survival to these patients. Also, CMC is considered a good spontaneous intermediate animal model for the research of human breast cancer (HBC), and therefore, the study of new treatments for CMC is a promising field in comparative oncology. Dogs with CMC have a comparable disease, an intact immune system, and a much shorter life span, which allows the achievement of results in a relatively short time. Besides conventional chemotherapy, innovative therapies have a large niche of opportunities. In this article, a comprehensive review of the current research in adjuvant therapies for CMC is conducted to gather available information and evaluate the perspectives. Firstly, updates are provided on the clinical–pathological approach and the use of conventional therapies, to delve later into precision therapies against therapeutic targets such as hormone receptors, tyrosine kinase receptors, p53 tumor suppressor gene, cyclooxygenases, the signaling pathways involved in epithelial–mesenchymal transition, and immunotherapy in different approaches. A comparison of the different investigations on targeted therapies in HBC is also carried out. In the last years, the increasing number of basic research studies of new promising therapeutic agents on CMC cell lines and CMC mouse xenografts is outstanding. As the main conclusion of this review, the lack of effort to bring the in vitro studies into the field of applied clinical research emerges. There is a great need for well-planned large prospective randomized clinical trials in dogs with CMC to obtain valid results for both species, humans and dogs, on the use of new therapies. Following the One Health concept, human and veterinary oncology will have to join forces to take advantage of both the economic and technological resources that are invested in HBC research, together with the innumerable advantages of dogs with CMC as a spontaneous animal model.

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“…Spontaneously occurring canine mammary tumors share some common molecular characteristics and biological behavior with that of human breast cancer (28). This would lead to the strong consideration of a canine mammary tumor model being a more appropriate or ideal model for human breast cancer (29) as opposed to a murine model, for example, which is induced and does not spontaneously occur.…”

Section: Discussionmentioning

confidence: 99%

A Novel Canine Mammary Cancer Cell Line: Preliminary Identification and Utilization for Drug Screening Studies

Sun

et al. 2021

Front. Vet. Sci.

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Canine malignant mammary tumor is a dangerously fatal neoplastic disease with poor survival in female dogs. The aim of this study was to preliminary characterize a novel canine mammary cancer cell line, B-CMT, from canine primary mammary gland tumor, and to utilize it as a cell model for in vitro screening of possible therapeutic drugs. The successfully established cell line, B-CMT, was cultured over 50 passages. B-CMT has a fast proliferation rate, and a population doubling time (PDT) of 33.6 h. The B-CMT cell line lacked human epidermal growth factor receptor-2 (HER-2), estrogen receptors (ER) and progesterone receptors (PR) expression by qRT-PCR. Compared with MDCK cells, CDH1 expression of CMT cell line was significantly decreased or even absent, but GATA3 expression dramatically increased, while TGF-β expression was at a similar level. Interestingly, the B-CMT cell line from canine primary tumor also showed positive hypoxia inducible factor-1α (HIF-1α) results in immunofluorescence (IF), western blot, and qRT-PCR analysis. Ten days post inoculation with EGFP-B-CMT (B-CMT cells stably expressing EGFP), the experimental mice developed palpable soft tissue masses which histologically resembled the canine primary tumor, and was approved to be derived from B-CMT cell line through detection of EGFP by immunohistochemical (IHC) analysis. Moreover, we investigated the cytotoxicity of five drugs to B-CMT cells, and the results showed that rapamycin and imatinib significantly inhibited the proliferation of the cells in vitro within a certain range of concentration. They also induced cell cycle arrest of B-CMT cells at G1 and G2 phase, respectively. In summary, the results of this report showed that B-CMT cell line might serve as a tool for future studies on tumor microenvironment and drug resistance.

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Quantitative analysis of HER2 mRNA expression by RNA in situ hybridization in canine mammary gland tumors: Comparison with immunohistochemistry analysis

Cited by 22 publications

References 43 publications

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines With Vasculogenic Mimicry Ability in vitro and in vivo

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines With Vasculogenic Mimicry Ability in vitro and in vivo

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

A Novel Canine Mammary Cancer Cell Line: Preliminary Identification and Utilization for Drug Screening Studies

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