Establishment of a lung metastatic breast tumor xenograft model in nude rats.
OBJECTIVE
Larger animal models provide relevant tumor burden in the development of advanced clinical imaging methods for non-invasive cancer detection and diagnosis, and are especially valuable for studying metastatic disease. Most available experimental models, however, are based on immune-compromised mice. To lay the foundation for studying spontaneous metastasis using non-invasive magnetic resonance imaging (MRI), this study aims to establish a highly metastatic breast cancer xenograft model in nude rats.


METHODS
A highly metastatic variant of human adenocarcinoma MDA-MB-231 known as LM2 was inoculated into nude rats. Orthotopic and subcutaneous (flank) sites were compared, with half of the orthotopic injections guided by ultrasound imaging. MRI with gadolinium contrast administration was performed weekly beginning on Day 6 and ending on Day 104. Excised tumors were assessed on histology using hematoxylin and eosin and CD34. Fisher's exact test was used to compare successful tumor induction amongst different inoculation methods.


RESULTS
Primary LM2 tumors were established orthotopically in all cases under ultrasound-guided injection, and none otherwise (p = 0.0028). Contrast-enhanced MRI revealed rapidly progressing tumors that reached critical size (15 mm diameter) in 2 to 3 weeks after inoculation. MRI and histology findings were consistent: LM2 tumors were characterized by low vascularity confined to the tumor rim and large necrotic cores with increasing interstitial fluid pressure.


CONCLUSIONS
The metastatic LM2 breast tumor model was successfully established in the mammary fat pads of nude rats, using ultrasound needle guidance as a non-invasive alternative to surgery. This platform lays the foundation for future development and application of MRI to study spontaneous metastasis and different stages throughout the metastatic cascade.
The Research Institute and Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Joris Tchouala
JT
Nofiele
The Research Institute and Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; The Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
Hai-Ling Margaret
HL
Cheng
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D051381:Rats; D011923:Rats, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods*