Characterization of CC-531 as a Rat Model of Colorectal Liver Metastases

Abstract

PurposeSurgical resection of colorectal liver metastases is not achievable in more than 70% of the cases. Although the liver directed therapies have become a part of the stand of care, lack of a preclinical model impedes the assessment of toxicity and therapeutic benefits attributed several candidate drugs or treatment regimens that can be designed. In the present study we aim develop and characterize a rat colorectal liver metastasis model.Materials and MethodsGrowth characteristics of CC-531 cells were determined in vitro followed by subcapsular liver implantation in syngeneic WAG/Rij rats. Tumor growth progression was followed over 3 weeks by ultrasound (US) and magnetic resonance imaging (MRI). Growth characteristics were also assessed by histopathology and immunohistochemistry in harvested tumor tissues.ResultsThe doubling time of CC-531 cells was found be under 24hrs and all the implanted rats grew tumors. US imaging showed hypoechoic masses and MRI showed contrast enhancement representing complex tumor microenvironments. Hematoxylin and Eosin staining confirmed tumor growth and uniform CD31 staining in tumor confirmed even vessel density.ConclusionCC-531 can be used as a metastatic rat tumor colorectal liver metastases model with well-defined characteristics that can be readily followed by imaging whilst having a therapeutic window for interventions.

Localized and triggered release of oxaliplatin for the treatment of colorectal liver metastasis

“…CC-531 cell line was cultured as described elsewhere 24 . Cells (3×10 4 ) plated in 96 wells were divided into different groups and exposed to an alternating magnetic field (~1.85 kW, 200 kHz) for 5 minutes at every hour for 6 hrs and at 24, 48, 72 and 96 hrs.…”

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

“…An ideal animal CRC model should allow the development of local tumors, it should replicate all stages of CRC evolution, permit the assessment of the disease progression with radiology and endoscopic methods, (it should allow us to) understand the toxicities related with therapeutic procedures, and be largely adjustable to laboratories without surgical knowledge, enabling its replication . However, the development of animal models is an arduous work, depending majorly on the strain of animals and cancer cells that are used …”

“…This model reveals greater efficiency than sporadic CRC models, but the income on tumor formation is still far from the ideal. However, this model type had its efficiency greatly improved with the creation of genetic mouse models, but even so, in some cases, when the metastases are detected, the animals are too ill to expose them to therapeutic options …”

“…But like other models, the xenograft model has its limitations, one of them, the low metastatic capacity, reason that motivated some researchers to try new approaches like injection into the spleen, portal vein, and liver . The liver injection model does not represent a metastatic model but rather a heterotopic implantation of colon cancer cells and the spleen and portal vein injection models result in highly infiltrative tumors that impair the possibility of radiological characterization and treatment approaches …”

“…In spite of the progress in clinical and biological knowledge, CRC remains a main public health issue, and despite the rapid development of treatments in the last years, the mortality rate related to this type of cancer remains high, especially in the advanced stages of disease . About half of the patients with CRC will develop liver metastases, and from that subpopulation only 25% are eligible for surgery with curative intent …”