Abstract
Xenografts can grow in immunosuppressed hosts, such as SCID mice, and tumor material can be injected into hosts either ectopically or orthotopically. Choosing the correct model to use is a crucial step in animal research. The aim of this study was to report the differences between ectopic and orthotopic xenografts in tumor progression, metastasis capacity, histological features, and steroid hormone profiles in xenografts from the cIMC (canine inflammatory mammary cancer) cell line IPC-366 and hIBC (human inflammatory breast cancer) cell line SUM149. To achieve this purpose, 40 female mice 6–8 weeks old were inoculated with IPC-366 and SUM149 cells subcutaneously (ectopic models) or into mammary fat pad (orthotopic models). Mice were monitored for tumor progression and appearance of metastases, and generated tumors were analyzed in terms of histological examination and steroid hormone production. The results revealed differences in tumor appearance and percentage of metastasis between ectopic and orthotopic models, which were higher in the ectopic xenografts from both cell lines. However, both models had similar characteristics of tumor progression, histological features, and steroid hormone secretion profiles. We show that the ectopic model can be validated as a good and useful model of tumor development in addition to, not contrary to, the orthotopic model in breast cancer research.
Highlights
Human and canine inflammatory breast cancer are the most aggressive mammary neoplasms that affects women [1,2,3] and female dogs [4,5]. hIBC accounts for around 6%of human breast cancer diagnoses, presenting poor survival in women, and cIMC is more prevalent than hIBC [1,4,6]
In the early 1970s, it was demonstrated that human tumor tissues could be successfully grown in athymic nu/nu mice, leading to ectopic tumor xenografts becoming a valuable approach to the study of cancer biology [16,17,19,20]
Specific types of tumor models in rodents include ectopic xenografts of tumor-derived cell lines and orthotopic xenografts in which tumor cell lines are implanted into the primary tumor source [16,17,19]
Summary
Of human breast cancer diagnoses, presenting poor survival in women, and cIMC is more prevalent than hIBC (approximately 7.6%) [1,4,6]. These diseases are characterized by the invasion of dermal lymphatic vessels by neoplastic cells, which blocks lymph drainage and causes the characteristic edema [1,4,7]. This type of cancer is highly angiogenic and angioinvasive in both species [1,8,9,10]. The IPC-366 cell line, the first canine inflammatory mammary cancer triple-negative cell line, has been established and characterized [1,14]
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