TiHo-0906: a new feline mammary cancer cell line with molecular, morphological, and immunocytological characteristics of epithelial to mesenchymal transition

Granados-Soler, José Luis; Junginger, Johannes; Hewicker‐Trautwein, M.; Bornemann-Kolatzki, Kirsten; Beck, Julia; Brenig, Bertram; Betz, Daniela Simon; Schille, Jan Torben; Escobar, Hugo Murua; Nolte, Ingo

doi:10.1038/s41598-018-31682-1

Cited by 7 publications

(16 citation statements)

References 99 publications

(146 reference statements)

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“…Interestingly, the Jak-STAT signalling pathway was the only KEGG pathway enriched with amplified genes in the basal-like TN subtype. Finally, CNGs in F2 64-82.3 Mb (human homologue in HSA 8q) resemble a CNG reported in HBCs 18,41 , canine mammary tumours 82 , and HBC-and FMC-derived cell lines 19,83,84 . This region harbours more than 30 HBC-related genes 19,28,41 , among those MYC, SCRIB, NDRG1, and PTK2 are EMT-related genes frequently amplified in human cancer 21 .…”

Section: Discussionsupporting

confidence: 58%

“…Among CNGs detected, survival intervals remained negatively influenced by CNGs in B4 1-29 Mb and F2 64-82.3 Mb in the multivariate analysis. The influence of these aberrations on EMT-elicitation in an FMC-derived cell line was described for our group 84 . In this study, these CNGs were associated with poor outcomes and were commonly observed across the population except for the LA subtype.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival

Granados-Soler

Bornemann-Kolatzki²,

Beck³

et al. 2020

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Feline mammary carcinomas (FMCs) are highly malignant. As the disease-free survival (DFS) and overall survival (OS) are short, prognostication is crucial. Copy-number variations (CNVs) analysis by nextgeneration sequencing serves to identify critical cancer-related genomic regions. Thirty-three female cats with FMCs were followed during two years after surgery. Tumours represented tubulopapillary and solid carcinomas encompassing six molecular subtypes. Regardless of the histopathological diagnosis, molecular subtypes showed important differences in survival. Luminal A tumours exhibited the highest DFS (p = 0.002) and cancer-specific OS (p = 0.001), and the lowest amount of CNVs (p = 0.0001). In contrast, basal-like triple-negative FMCs had the worst outcome (DFS, p < 0.0001; and OS, p < 0.00001) and were the most aberrant (p = 0.05). In the multivariate analysis, copy-number losses (CNLs) in chromosome B1 (1-23 Mb) harbouring several tumour-repressors (e.g. CSMD1, MTUS1, MSR1, DBC2, and TUSC3) negatively influenced DFS. Whereas, copy-number gains (CNGs) in B4 (1-29 Mb) and F2 (64-82.3 Mb) comprising epithelial to mesenchymal transition genes and metastasis-promoting transcription factors (e.g. GATA3, VIM, ZEB1, and MYC) negatively influenced DFS and cancer-specific OS. These data evidence an association between specific CNVs in chromosomes B1, B4 and F2, and poor prognosis in FMCs.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival

Granados-Soler

Bornemann-Kolatzki²,

Beck³

et al. 2020

Sci Rep

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“…Epithelial to mesenchymal transition is a common pathological process in canine metastatic prostate cancer [90,91]. It is suggested that the analyzed cell lines and respective tumor tissues show features of epithelial to mesenchymal transition, as they express both epithelial (pan-CK, CK7, CK8/18, E-Cad) and mesenchymal (vimentin, Calp) markers concurrently [6,90]. Consequently, epithelial to mesenchymal transition is likely to be advanced in Adcarc1258, as its primary tumor does only express E-Cad as epithelial marker and even this feature gets lost in the cell line.…”

Section: Plos Onementioning

confidence: 99%

“…Consequently, epithelial to mesenchymal transition is likely to be advanced in Adcarc1258, as its primary tumor does only express E-Cad as epithelial marker and even this feature gets lost in the cell line. Adaption processes to culturing conditions or clonal selection of small proportions of tumor cells [6,92,93] may explain the further mesenchymal transition of cell lines Adcarc1508, TCC1509, Adcarc1511.1, Metadcarc1511.2 and Metadcarc1511.3, which is characterized by gains of vimentin and losses of pan-CK expression.…”

Section: Plos Onementioning

confidence: 99%

“…Ideally, investigated features of the primary tumor are representative for the tumor type or subtype and stay preserved in the derived cell line [4]. However, clonal selection and adaption to culturing conditions over multiple passages can affect features like gene expressions and sensitivities against chemotherapeutic acting drugs [4][5][6]. Accordingly, the matched characterization of cell lines and respective tissues of origin allows a comprehensive evaluation in which terms a cell line actually represents the tumor entity and can therefore be used as suitable model.…”

Section: Introductionmentioning

confidence: 99%

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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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