Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea

Abstract

Clearly new breast cancer models are necessary in developing novel therapies. To address this challenge, we examined mammary tumor formation in the Syrian hamster using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50 mg/kg intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A and HMAM4B, were derived from one of the primary mammary tumors induced by MNU. The morphology of the primary tumor was similar to a high-grade poorly differentiated adenocarcinoma in human breast cancer. The primary tumor stained positively for both HER-2/neu and pancytokeratin, and negatively for both cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor derived from HMAM4B cells implanted into a syngeneic hamster was further propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female syngeneic hamsters with a 70% take rate of tumor formation. These cells proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44). To determine responsiveness to the estrogen receptor (ER), a cell proliferation assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and human MCF-7 (ER positive) cells showed a similar decrease at 24 h. However, MDA-MB-231 (ER negative) cells were relatively insensitive to any decrease in proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell line was likely derived from a luminal B subtype of mammary tumor. These results also represent characterization of the first mammary tumor cell line available from the Syrian hamster. The HMAM5 cell line is likely to be useful as an immunocompetent model for human breast cancer in developing novel therapies.

Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches

“…); Group two—four male mice (3 animals died within 2 days after injection for an unknown reason) were treated once intraperitoneally (i.p.) with 100 mg/kg MNU in DMSO (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) [26,27,28,29]; Group three—four male and female mice each were treated once s.c. with 0.1 mL (5 mg/mL) MCA in sesame oil (Sigma-Aldrich Chemie GmbH, Steinheim, Germany) and once additionally with 0.025 mL intramuscularly (i.m.) on the right hind leg [30,31]; Group four—four male and female mice each were orally (p.o.)…”

Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy

“…Researchers have also used N-methyl-N-nitrosourea (MNU) to induce hamster breast cancer, and histopathological analysis showed that this animal model resembled human high-grade poorly differentiated breast adenocarcinoma. At the same time, they established the first immortalization of a Syrian hamster breast cancer cell line HMAM5, with a high tumorigenic rate in female hamsters (31). Additional carcinogen-induced cancers in Syrian hamsters include kidney cancer (51,54,55), cholangiocellular tumors (52), endometrial adenocarcinoma (56) and laryngeal cancer (57).…”

“…Additionally, the syngeneic Syrian hamster glioma orthotopic model showed hypercellularity and necrotic areas, consistent with the characteristics of human glioma (24). At present, the Syrian hamster syngeneic tumor models used for research include pancreatic cancer (25)(26)(27), oral cancer (28), gallbladder cancer (29), glioma (24), kidney cancer (23,30), liver cancer (23), lung cancer (23) and breast cancer (31). However, the challenge with all syngeneic tumor models is that they cannot reflect the multi-stage process of carcinogenesis due to the direct engraftment of malignant cells, therefore, these models are not suitable for the evaluation of the application of anti-tumor immunotherapy in the early stages of tumorigenesis (32).…”

Морфологічна Характеристика Новоутворень Молочної Залози В Декоративних Щурів

“…Новоутворення молочної залози є складним багатоетапним процесом, який може бути індукований хімічними речовинами, радіацією, вірусами або генетичними факторами. Частота виникнення пухлин, їх кількість на тварину, латентність та тип пухлини залежать від віку, статі, репродуктивної історії та ендокринологічного середовища господаря під час впливу канцерогену, а також дієти та дози канцерогену [1, 3,4,9,21,24]. Неоплазії молочної залози тварин на початковій стадії характеризуються ознаками, тому власники звертаються до фахівців за допомогою на запущеній стадії розвитку захворювання, коли, на жаль, досягнути повного одужання неможливо.…”