Tokyo University of Agriculture and Technology creates feline breast cancer tissue models showing similarities to human disease

Doctoral Student Haru Yamamoto of the Cooperative Department of Veterinary Medicine, Faculty of Agriculture, along with Associate Professor Tatsuya Usui and Professor Kazuaki Sasaki and their colleagues from the Division of Animal Life Science, Graduate School of Agriculture at Tokyo University of Agriculture and Technology (TUAT), successfully created three-dimensional organoids using tumor tissue from cats with breast cancer. These results demonstrate their usefulness as a model for studying disease. This is expected to lead to the elucidation of pathological mechanisms and development of new treatments for highly malignant feline breast cancer, as well as to be utilized for translational research into human breast cancer (HBC). The study was published online in Scientific Reports.

Feline breast cancer (FBC) is approximately 90% highly malignant, with a recurrence rate of about 80-90%, making it a highly refractory tumor. Currently, surgical treatment is the first-line treatment, with unilateral or bilateral mastectomy being performed. On the other hand, while chemotherapy is used as monotherapy or as an adjunct to surgery, no treatment method exists which reliably extends survival.

FBC research employs two-dimensional cell culture models which grow on flat surfaces in addition to mammosphere culture models with stem cell characteristics. In recent years, organoid culture methods have also been reported as a new culture model. Organoid culture is a three-dimensional cultivation method in which epithelial cells derived from organ tissue are mixed with Matrigel using a medium that enhances stemness.

The research group has previously developed various cancer organoid models including canine transitional cell carcinoma, prostate cancer, lung cancer, mesothelioma, and apocrine gland carcinoma. These models enable research to evaluate drug sensitivity and elucidate pathological mechanisms.

In this study, the researchers established an organoid culture method derived from FBC tissue and verified its usefulness as a culture tool. They also analyzed the relationship between pathways identified through RNA sequencing and the pathological mechanisms of FBC and HBC.

Three-dimensional organoid culture using tissue excised from cats with breast cancer resulted in the successful creation of FBC organoids from 32 cases. FBC organoids were mainly classified into the basal type with solid morphology and the luminal type with tabular morphology. The expression of morphology-specific markers was observed in each type. Using the same method, organoids were also created from normal feline mammary tissue (FNM). FBC organoids showed tumorigenicity in mice, and the group confirmed the similarity in marker expression with the original tissue. When FBC organoids were exposed to various anticancer drugs, they showed different sensitivities depending on the patient cat from which they were derived.

This revealed the FBC organoids are a culture model capable of evaluating differences in anticancer drug sensitivity among patient cats. Furthermore, when comparing gene expression in FBC and FNM organoids using RNA sequencing, it was found that the LMTK3/FADS2 pathway affects cell proliferation, invasion, and apoptosis, thus playing an important role in FBC progression. It was also discovered that LMTK3 and FADS2 mediate cell proliferation, invasion, and apoptosis in HBC cell lines and HBC organoids. The research determined the expression levels correlate with breast cancer progression.

The FBC organoid culture method has now been established. It is expected to be utilized as a culture model for identifying new therapeutic targets and elucidating the pathological mechanisms of FBC. Furthermore, this LMTK3/FADS2 pathway was shown to be a potential new therapeutic target not only in cats but also in humans. Since FBC and HBC share many similarities, there is potential for the FBC organoid model established in this study to be utilized for pathological analysis as part of translational research between animals and humans.

Journal Information
Publication: Scientific Reports
Title: Novel organoid-based exploration reveals the role of LMTK3/FADS2 signaling in metastatic breast cancer progression in felines and humans
DOI: 10.1038/s41598-025-28751-7