Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation

Abstract

A number of murine models are used to mimic the pathology of breast cancer. Tissue inoculation and cell inoculation using orthotopic implantation (OS) and subcutaneous implantation (SQ) are commonly used to generate murine models to investigate cancer. However, limited information is available in regard to the variations of these methods. The present study compared growth, metastasis, survival and histopathology of tumors produced using OS and SQ to characterize features of the tumors produced by the two distinct methods. Additionally, the present study aimed at providing increased options for investigators when designing experiments. 4T1-luc2 cell suspension or 4T1-luc2 tissue suspension was inoculated using either OS or SQ into BALB/c mice. Tumor growth and metastasis were detected using an in vivo imaging system and calipers. Excised tumors and lung were assessed by tissue staining with hematoxylin and eosin, and the vessel marker cluster of differentiation 31. The results of the present study revealed that the cell suspension generated breast tumors of increased size, which was visualized and determined, following inoculation, using calipers at an earlier time point compared with tumors produced by tissue suspension. The increasing bioluminescent trend of OS tumors was more marked compared with that of SQ tumors. The volume of OS tumor was increased with decreased variation, compared with that of SQ tumors. In addition, the OS tumor exhibited increased microvessel density. Bioluminescent signals and histological results in regard to metastasis were consistent: OS implantation produced increased lung metastasis compared with that of SQ implantation, although they exhibited similar survival times. The results of the present study indicated that the inocula from distinct sources (tissue or cell) affected tumor growth. Furthermore, breast tumor progression and histopathological characteristics were distinct between OS and SQ, whereas OS exhibited increased malignant behavior. Understanding the characteristics of murine breast cancer models established by diverse methods may aid investigators to select appropriate animal models, according to the requirements of the study.

Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In�vitro and in�vivo studies

“…A total of 30 female BALB/c mice (age, 6-8 weeks; weight, 18±2 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and housed under specific pathogen-free conditions at a constant temperature (20±2°C) and 40-50% humidity in a 12-h light/dark cycle with free access to food and water. The 4T1 orthotopic mammary tumor model was established as previously described ( 41 , 44 ). Briefly, 1×10 4 4T1 cells were injected into the left fourth mammary fat pad during isoflurane gas anesthesia.…”

[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

“…It is interesting to note that a relation between tumor volume and radiotracer uptake was demonstrated in subcutaneous xenograft models but not in the orthotopic model. As already reported by several studies, the microenvironment of orthotopic implantation may be more favorable to tumor development [26]. In a second time, we performed the evaluation of early response to paclitaxel by [ 18 F]ML-10 and [ 18 F]FDG PET imaging on MDA-MB-468 xenograft models.…”

“…Indeed, the malonic acid moieties of this radiotracer have pKa values of 3.07 and 5.78. At physiological pH, the di-anionic form of malonate predominates [20,26,[28][29][30]. According to pKa values cited, a decrease of extracellular pH will favor the apparition of the mono-protonated carboxylic acid form of [ 18 F]ML-10 and facilitate its interaction with the membrane of the apoptotic cells [30].…”

“…Nevertheless, this phenomenon was not observed in the orthotopic model. Zhang's team was able to show that an orthotopic implantation revealed a more favorable and homogeneous growth of tumors as well as an increased microvessel density [26]. A better tumor vascularization then allows a better elimination of necrotic cells and therefore a less important variation in pH.…”

Curcumin combined with Glu-GNPs enhancing radiosensitivity of transplanted tumor of MDA-MB-231-luc cells in nude mice

“…In addition, it can be accurately detected in vivo without killing mice [6] . Zhang et al [7] found that the results of in vivo imaging and pathological detection are consistent, but compared with HE staining, the growth and metastasis of breast cancer can be more directly and clearly observed using in vivo imaging system. In vivo imaging method is applied to study transplanted tumor in mice.…”