Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours. Part 2: Invasion, angiogenesis, metastasis and therapy

Santos, Andreia; Matos, Augusto J. F. de

doi:10.1016/j.tvjl.2015.03.029

Cited by 11 publications

(21 citation statements)

References 108 publications

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“…The anatomy of the normal mammary gland is similar in dogs and women. The alveoli and ducts of the mammary gland consist of luminal epithelial cells lined by myoepithelial cells and are separated from the surrounding connective tissue by the basement membrane (Liu et al, 2014;Santos and Matos, 2015). In both species tumor formation is seen as a dynamic process starting from benign hyperplastic lesions that can evolve into a carcinoma in situ.…”

Section: Canine Mammary Tumors As a Model For Human Breast Cancermentioning

confidence: 99%

“…In a further step, these tumors can become invasive, which is marked by the disruption of the basement membrane and potential seeding of metastases (Gilbertson et al, 1983;Burstein et al, 2004;Simpson et al, 2005;Sorenmo et al, 2009). On a molecular level, many of the key alterations in human breast cancer are faithfully recapitulated in CMTs, including germline mutations in BRCA1, BRCA2, and TP53 that are associated with an enhanced risk of hereditary cancer in humans (Liu et al, 2014;Matos and Santos, 2015;Santos and Matos, 2015;Schiffman and Breen, 2015). And finally, besides clinical factors such as tumor size, lymph node involvement, and clinical stage, the prognostic value of histo-pathological aspects such as tumor type and grade, and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) is conserved between canine and human breast cancer (Rivera et al, 2009;Queiroga et al, 2011b;Sleeckx et al, 2011;Lahkhani et al, 2012;Rasotto et al, 2012Rasotto et al, , 2017Im et al, 2013;Pena et al, 2013;Nguyen et al, 2017).…”

Section: Canine Mammary Tumors As a Model For Human Breast Cancermentioning

confidence: 99%

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Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

Markkanen

2019

Front. Cell Dev. Biol.

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Spontaneous canine simple mammary tumors (CMTs) are often viewed as models of human breast cancer. Cancer-associated stroma (CAS) is central for initiation and progression of human cancer, and is likely to play a key role in canine tumors as well. Until recently, however, canine CAS in general, and in CMT in particular, lacked detailed characterization and it remained unclear how canine and human CAS compare. This void in knowledge regarding canine CAS and the resulting lack of unbiased crossspecies analysis of molecular homologies and differences undermined the validity of the canine model for human disease. To assess stromal reprogramming in canine breast tumors, we have recently established a protocol to specifically isolate and analyze CAS and matched normal stroma from archival, formalin-fixed paraffin embedded (FFPE) clinical tumor samples using laser-capture microdissection followed by next-generation RNA-sequencing. Using this approach, we have analyzed stromal reprogramming in both malignant canine mammary carcinomas (mCAs) as well as benign canine mammary adenomas in a series of studies. Our results demonstrate strong stromal reprogramming in CMTs and identify high-grade molecular homology between human and canine CAS. Here, I aim to give a short background on the value of comparative oncology in general, and spontaneous CMT in particular. This will be followed by a concise review of the current knowledge of stromal reprogramming in both malignant canine mCA and benign adenoma. Finally, I will conclude with insights on highly conserved aspects of stromal reprogramming between CMT and human breast cancer that accentuate the relevance of CAS in CMT as a model for the human disease.

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Section: Canine Mammary Tumors As a Model For Human Breast Cancermentioning

confidence: 99%

Section: Canine Mammary Tumors As a Model For Human Breast Cancermentioning

confidence: 99%

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

Markkanen

2019

Front. Cell Dev. Biol.

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“…Retrospective studies exploring cytotoxic agents are mostly restricted to a limited number of dogs, included in the respective studies. Complex prospectivly conducted studies evaluating experimental therapeutic protocols are practically missing [32]. However, the establishment of non-invasive therapeutic approaches for mammary carcinomas is currently addressed in various ways.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines

Hammer

Becker

Rateitschak

et al. 2016

IJMS

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Human and canine mammary tumours show partial claudin expression deregulations. Further, claudins have been used for directed therapeutic approaches. However, the development of claudin targeting approaches requires stable claudin expressing cell lines. This study reports the establishment and characterisation of canine mammary tissue derived cell lines, analysing longitudinally the claudin-1, -3, -4 and -7 expressions in original tissue samples, primary cultures and developed cell lines. Primary cultures were derived from 17 canine mammary tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour and benign mixed tissue. Cultivation was performed, if possible, until passage 30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin expression was analysed immunocytochemically. Cultivation resulted in 11 established cell lines, eight showing epithelial character. In five of the early passages the claudin expressions decreased compared to the original tissues. In general, claudin expressions were diminished during cultivation. Three cell lines kept longitudinally claudin, as well as epithelial marker expressions, representing valuable tools for the development of claudin targeted anti-tumour therapies.

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“…E‐cadherin (codified by CHD1 ) is a cell adhesion molecule expressed in epithelial tissues that promote cell adhesion in adjacent cells . It has shown that loss of its cytoplasm membrane expression is associated with lymph node metastasis, high invasiveness, recurrence and poor prognostic . Progression to metastasis is a multistep process that involves the acquisition of invasive attributes .…”

Section: Discussionmentioning

confidence: 99%

“…13 -15 Survival of dogs suffering from CMT is mainly dependent on the occurrence of metastases. 13,14 In addition to the established histological classifications and clinical staging, many new molecular markers have been evaluated for their predictive value in terms of metastatic action and reduced survival, such as steroid receptors, markers of cell adhesion or proliferation. 16 However, the description of metastatic potential in CMT is still based on histological, clinical and radiographic examination, which can only report dissemination of tumour cells that already took place.…”

Section: Introductionmentioning

confidence: 99%

A three‐dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators

Cardoso

Sakamoto

Stockmann

et al. 2016

Vet Comparative Oncology

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In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two-dimensional (2D) and three-dimensional (3D) conditions. The 3D was performed in six-well AlgiMatrix™ (LifeTechnologies®, Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50-125 µm for CC and 175-200 µm for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases-1, -2, -9 and -13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E-cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)-derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model.

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Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours. Part 2: Invasion, angiogenesis, metastasis and therapy

Cited by 11 publications

References 108 publications

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines

A three‐dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators

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