The Dog as a Natural Animal Model for Study of the Mammary Myoepithelial Basal Cell Lineage and its Role in Mammary Carcinogenesis

Rasotto, Roberta; Goldschmidt, Michael H.; Castagnaro, Massimo; Carnier, Paolo; Caliari, D.; Zappulli, Valentina

doi:10.1016/j.jcpa.2014.04.013

Cited by 36 publications

(42 citation statements)

References 64 publications

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“…In human breast cancer, several authors have showed that VDR protein expression declines in highly aggressive tumours . Furthermore, the well‐differentiated ME cells appear to be the canine mammary cell type that exhibits greater VDR expression, pointing to the presence of ME cells with different phenotypic characteristics in malignant tumours as formerly reported in the canine and human species …”

Section: Discussionmentioning

confidence: 66%

“…The normal ductal and lobular system of the mammary gland is lined by 2 distinct epithelial cell layers: the inner or luminal epithelial (LE) cell layer and an outer layer composed of myoepithelial (ME) cells. Canine mammary tumours have been suggested as a potential suitable model for studies in human breast cancer research due to the great number of similarities between them . Both human and canine mammary gland are hormone dependent; that is, they are strongly influenced by ovarian hormones, mainly oestrogen (E) and progesterone (P), which act through binding to its E receptor (ER) and P receptor (PR), respectively, and they are traditional prognostic and predictive factors in both species …”

Section: Introductionmentioning

confidence: 99%

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Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Sánchez-Céspedes

Fernández-Martínez

Raya

et al. 2017

Vet Comparative Oncology

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The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Sánchez-Céspedes

Fernández-Martínez

Raya

et al. 2017

Vet Comparative Oncology

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“…Rasotto et al characterized normal canine mammary epithelium by detailed and quantitative immunohistochemistry analysis and proposed a hierarchy in which mammary progenitors comprise 3% of the total basal epithelial population and express the following phenotype: CK5 + /CK14 + /p63 + /vimentin + /SMA – /CALP – /CK8/18 – . The function of this subpopulation has not been confirmed in vitro or in vivo yet, as these markers are intracellular and do not enable isolation and characterization of live cells . Two other studies reported that primary canine mammary epithelial cells are able to form colonies in suspension (mammospheres), representing the stem cell property of anchorage‐independent growth .…”

Section: Characterization Of Mammary Stem Cellsmentioning

confidence: 99%

Conserved and variable: Understanding mammary stem cells across species

2017

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Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate the mammary epithelium with each cycle of lactation. These long-lived, tissue-resident MaSC are also targets for malignant transformation and may be cancer cells-oforigin. Consequently, MaSC are extensively researched in relation to their role and function in development, tissue regeneration, lactation, and breast cancer. The basic structure and function of the mammary gland are conserved among all mammalian species, from the most primitive to the most evolved. However, species vary greatly in their lactation strategies and mammary cancer incidence, making MaSC an interesting focus for comparative research. MaSC have been characterized in mice, to a lesser degree in humans, and to an even lesser degree in few additional mammals. They remain uncharacterized in most mammalian species, including "ancient" monotremes, marsupials, wild, and rare species, as well as in common and domestic species such as cats. Identification and comparison of MaSC across a large variety of species, particularly those with extreme lactational adaptations or low mammary cancer incidence, is expected to deepen our understanding of development and malignancy in the mammary gland. Here, we review the current status of MaSC characterization across species, and underline species variations in lactation and mammary cancer through which we may learn about the role of MaSC in these processes. V C 2017 International Society for Advancement of Cytometry

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“…FFPE tissues and FFPE embedded cell pellets of three consecutive passages were immunohistochemically stained with mouse monoclonal antibodies raised against pan-cytokeratin (pan-CK, detecting CK1, CK5, CK10, CK14), CK7, CK8/18, uroplakin III (UPIII), vimentin, E-Cadherin (E-Cad) and Calponin (Calp) and p53, as well as goat polyclonal IgG detecting COX-2 (S2 Table). Cross reactivity with canine tissue was either declared by the manufacturers or based on the literature [59][60][61][62] as summarized in S2 Table. If not described otherwise, all incubation steps were performed at room temperature. For antigen retrieval, slides were cooked in citrate buffer by microwave for 20 minutes or digested by proteinase K for 40 minutes for the CK7 antibody.…”

Section: Comparative Characterization Of Cellular Origin P53 and Coxmentioning

confidence: 99%

Characterization of six canine prostate adenocarcinoma and three transitional cell carcinoma cell lines derived from primary tumor tissues as well as metastasis

et al. 2020

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Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) of prostate and urinary bladder are highly invasive and metastatic tumors of closely neighbored organs. Cell lines are valuable tools to investigate tumor mechanisms and therapeutic approaches in vitro. PAC in dogs is infrequent, difficult to differentiate from TCC and usually characterized by poor prognosis, enhancing the value of the few available cell lines. However, as cell lines adapt to culturing conditions, a thorough characterization, ideally compared to original tissue, is indispensable. Herein, six canine PAC cell lines and three TCC cell lines were profiled by immunophenotype in comparison to respective original tumor tissues. Three of the six PAC cell lines were derived from primary tumor and metastases of the same patient. Further, two of the three TCC cell lines were derived from TCCs invading into or originating from the prostate. Cell biologic parameters as doubling times and chemoresistances to commonly used drugs in cancer treatment (doxorubicin, carboplatin and meloxicam) were assessed. All cell lines were immunohistochemically close to the respective original tissue. Compared to primary tumor cell lines, metastasis-derived cell lines were more chemoresistant to doxorubicin, but equally susceptive to carboplatin treatment. Two cell lines were multiresistant. COX-2 enzyme activity was demonstrated in all cell lines. However, meloxicam inhibited prostaglandin E2 production in only seven of nine cell lines and did neither influence metabolic activity, nor proliferation. The characterized nine cell lines represent excellent tools to investigate PAC as well as TCC in prostate and urinary bladder of the dog. Furthermore, the profiled paired cell lines from PAC primary tumor and metastasis provide the unique opportunity to investigate metastasis-associated changes PAC cells undergo in tumor progression. The combination of nine differently chemoresistant PAC and TCC cell lines resembles the heterogeneity of canine lower urinary tract cancer. Funding: The authors wish to thank the Studienstiftung des Deutschen Volkes for supporting EMP with a scholarship. This publication was supported by Deutsche Forschungsgemeinschaft and University of PLOS ONE Canine prostate and bladder cancer cell lines derived from primary tumor and metastasis PLOS ONE | https://doi.org/10.Original tissue (P = Prostate, B = urinary bladder, Ln = lymph node); cell lines' names are explained as institution (Tiho = University of Veterinary Medicine Hannover); species (D = dog); tissue origin (Pro = prostate; Urt = urinary tract (urinary bladder)); diagnosis (Adcarc = adenocarcinoma; Carc = carcinoma; Metadcarc = metastasis of an adenocarcinoma); abbreviations of cell lines written in bold; none = cell lines have not been published yet; n.a. = tissue of patient no. 5 is missing, as the patient owners declined surgery and necropsy; � diagnosis by cytology of cells obtained by fine needle aspiration biopsy.

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The Dog as a Natural Animal Model for Study of the Mammary Myoepithelial Basal Cell Lineage and its Role in Mammary Carcinogenesis

Cited by 36 publications

References 64 publications

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Conserved and variable: Understanding mammary stem cells across species

Characterization of six canine prostate adenocarcinoma and three transitional cell carcinoma cell lines derived from primary tumor tissues as well as metastasis

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