Mapping Mammary Tumor Traits in the Rat

Flister, Michael J.; Joshi, Amit; Bergom, Carmen; Rui, Hallgeir

doi:10.1007/978-1-4939-9581-3_12

Cited by 4 publications

(7 citation statements)

References 110 publications

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“…Such differences in the rat mammary tumors induced by DMBA and NMU could be due to their distinct mechanisms of action [153]. Though both agents rely on DNA alkylation to prompt tumor development, DMBA, unlike NMU, is considered an indirect alkylating agent, as it relies on the metabolic activation by hepatic cytochrome P450 enzymes.…”

Section: Disadvantagesmentioning

confidence: 99%

Rat Models of Hormone Receptor-Positive Breast Cancer

Nicotra,

Lutz,

Messal

et al. 2024

J Mammary Gland Biol Neoplasia

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Hormone receptor-positive (HR+) breast cancer (BC) is the most common type of breast cancer among women worldwide, accounting for 70–80% of all invasive cases. Patients with HR+ BC are commonly treated with endocrine therapy, but intrinsic or acquired resistance is a frequent problem, making HR+ BC a focal point of intense research. Despite this, the malignancy still lacks adequate in vitro and in vivo models for the study of its initiation and progression as well as response and resistance to endocrine therapy. No mouse models that fully mimic the human disease are available, however rat mammary tumor models pose a promising alternative to overcome this limitation. Compared to mice, rats are more similar to humans in terms of mammary gland architecture, ductal origin of neoplastic lesions and hormone dependency status. Moreover, rats can develop spontaneous or induced mammary tumors that resemble human HR+ BC. To date, six different types of rat models of HR+ BC have been established. These include the spontaneous, carcinogen-induced, transplantation, hormone-induced, radiation-induced and genetically engineered rat mammary tumor models. Each model has distinct advantages, disadvantages and utility for studying HR+ BC. This review provides a comprehensive overview of all published models to date.

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Section: Disadvantagesmentioning

confidence: 99%

Rat Models of Hormone Receptor-Positive Breast Cancer

Nicotra,

Lutz,

Messal

et al. 2024

J Mammary Gland Biol Neoplasia

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“…Unlike animals with spontaneous tumors, where the information is not clear, several studies with chemically induced female rat mammary tumors have described that tumor incidence is higher in thoracic region and in right mammary chain [ 101 , 102 ]. In summary, multiple factors, including gender, genetic background, age and parity, influence the susceptibility of rat mammary glands to the carcinogens MNU and DMBA [ 103 ]. Although also susceptible to these carcinogens, mice are not frequently used as models of chemically induced mammary cancer, probably due to their small size.…”

Section: Breast/mammary Cancermentioning

confidence: 99%

“…For example, following exposure to the carcinogen, tumor formation can be closely monitored on a weekly basis through manual palpation. After tumor diagnosis, this close follow-up allows several types of data to be obtained, such as overall incidence, latency and multiplicity (i.e., number of tumors per rat) [ 103 ]. At the end of the experiment, mammary tumors are collected, weighed, and stored/processed for various analyses, including histopathology [ 103 ] and omics-based analysis [ 204 , 205 ], among others.…”

Section: Advantages and Disadvantages Of Spontaneous Tumors And Induc...mentioning

confidence: 99%

“…After tumor diagnosis, this close follow-up allows several types of data to be obtained, such as overall incidence, latency and multiplicity (i.e., number of tumors per rat) [ 103 ]. At the end of the experiment, mammary tumors are collected, weighed, and stored/processed for various analyses, including histopathology [ 103 ] and omics-based analysis [ 204 , 205 ], among others. Lastly, the use of female rats as a mammary cancer model must be approved by the appropriate authorities for the protection of animals used for scientific purposes, and all legal aspects should be respected [ 5 ].…”

Section: Advantages and Disadvantages Of Spontaneous Tumors And Induc...mentioning

confidence: 99%

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Mammary Glands of Women, Female Dogs and Female Rats: Similarities and Differences to Be Considered in Breast Cancer Research

Ferreira

Gama

Seixas

et al. 2023

Veterinary Sciences

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Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory context. Both female dogs and female rats have contributed to the advancement of scientific knowledge in this field, and, in a “One Health” approach, they have allowed broad understanding of specific biopathological pathways, influence of environmental factors and screening/discovery of candidate therapies. This review aims to clearly showcase the similarities and differences among woman, female dog and female rat concerning to anatomical, physiological and histological features of the mammary gland and breast/mammary cancer epidemiology, in order to better portray breast tumorigenesis, and to ensure appropriate conclusions and extrapolation of results among species. We also discuss the major aspects that stand out in these species. The mammary glands of female dogs and women share structural similarities, especially with respect to the lactiferous ducts and lymphatic drainage. In contrast, female rats have only one lactiferous duct per nipple. A comprehensive comparison between humans and dogs is given a special focus, as these species share several aspects in terms of breast/mammary cancer epidemiology, such as age of onset, hormonal etiology, risk factors, and the clinical course of the disease. Holistically, it is clear that each species has advantages and limitations that researchers must consider during the development of experimental designs and data analysis.

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“…Previous research has localized inherited modifier(s) of TME vascular heterogeneity to RNO3 by CXM mapping and further narrowed by congenic mapping to a 36 Mb locus containing Dll4 alleles with distinct vascular expression patterns in the SS.BN3 IL2Rγ− consomic (Dll4−) and SS IL2Rγ− (Dll4+) rat strains, and verified via species-specific RNA sequencing and immunohistochemistry that strains inheriting the SS Dll4 allele on chromosome 3 have higher Dll4 expression on tumor-associated endothelium and that the blood vessel tortuosity and dysfunction increased in Dll4− strains [38,39]. Since there are many other candidate alleles on chromosome 3 that could also potentially account for the observed differences in therapeutic efficacy between the SS.BN3 IL2Rγ− and SS IL2Rγ− strains [38], to further investigate the potential contribution of Dll4 to inherited tumor vascular heterogeneity, eight novel SS.BN3 IL2Rγ− congenic xenograft host strains (CG1 to CG8) were constructed by introgression of the F1 progeny and F2 generation to capture different regions of RNO3 by marker-assisted selection, as described previously [50,53]. The exclusion congenic mapping localized a 7.9 Mb candidate region (marked by the SSLP marker D3Mgh11) that was associated with inherited tumor vascular heterogeneity and contained the Dll4 locus.…”

Section: Animalsmentioning

confidence: 99%

Dynamic NIR Fluorescence Imaging and Machine Learning Framework for Stratifying High vs. Low Notch-Dll4 Expressing Host Microenvironment in Triple-Negative Breast Cancer

Shafiee

Jagtap

Zayats

et al. 2023

Cancers

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Delta like canonical notch ligand 4 (Dll4) expression levels in tumors are known to affect the efficacy of cancer therapies. This study aimed to develop a model to predict Dll4 expression levels in tumors using dynamic enhanced near-infrared (NIR) imaging with indocyanine green (ICG). Two rat-based consomic xenograft (CXM) strains of breast cancer with different Dll4 expression levels and eight congenic xenograft strains were studied. Principal component analysis (PCA) was used to visualize and segment tumors, and modified PCA techniques identified and analyzed tumor and normal regions of interest (ROIs). The average NIR intensity for each ROI was calculated from pixel brightness at each time interval, yielding easily interpretable features including the slope of initial ICG uptake, time to peak perfusion, and rate of ICG intensity change after reaching half-maximum intensity. Machine learning algorithms were applied to select discriminative features for classification, and model performance was evaluated with a confusion matrix, receiver operating characteristic curve, and area under the curve. The selected machine learning methods accurately identified host Dll4 expression alterations with sensitivity and specificity above 90%. This may enable stratification of patients for Dll4 targeted therapies. NIR imaging with ICG can noninvasively assess Dll4 expression levels in tumors and aid in effective decision making for cancer therapy.

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Mapping Mammary Tumor Traits in the Rat

Cited by 4 publications

References 110 publications

Rat Models of Hormone Receptor-Positive Breast Cancer

Rat Models of Hormone Receptor-Positive Breast Cancer

Mammary Glands of Women, Female Dogs and Female Rats: Similarities and Differences to Be Considered in Breast Cancer Research

Dynamic NIR Fluorescence Imaging and Machine Learning Framework for Stratifying High vs. Low Notch-Dll4 Expressing Host Microenvironment in Triple-Negative Breast Cancer

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