Metastasis Models

The B16-F10 syngeneic melanoma model can be adapted to investigate primary tumor growth, therapeutic response and metastatic disease in immunocompetent C57BL/6 mice. Studies at Oncodesign Services have evaluated how implantation site, treatment timing and route of inoculation can be selected according to the experimental objective.

Demonstrated here, the B16-F10 melanoma model was implanted intravenously with lung tumor colonies measured at endpoint. Cyclophosphamide, a chemotherapy, successfully inhibited significant lung metastasis, when compared with the control:

For primary tumor studies, comparison of subcutaneous (SC) and mammary fat pad (MFP) implantation showed progressive tumor growth with both approaches, while MFP implantation significantly reduced tumor necrosis compared with the SC model.

The SC model has been characterized across multiple therapeutic modalities, including immune checkpoint inhibitors, STING agonists, chemotherapy and fractionated radiotherapy. Importantly, studies with anti-PD-1 and anti-CTLA-4 showed different responses depending on whether treatment began before or after an established tumor microenvironment was present, demonstrating how treatment timing can influence observed efficacy. Radiotherapy studies also demonstrated a dose-dependent response, while chemotherapy studies captured outcomes including tumor growth inhibition, relapse following treatment cessation and treatment-associated changes in body weight.

For metastatic research, intravenous inoculation can be used to establish lung metastases, with metastatic burden assessed through macroscopic analysis and qPCR. This configuration has been used both to investigate immune mechanisms involved in metastatic control and to evaluate therapeutic response. NK-cell depletion increased lung metastases, while Cyclophosphamide reduced metastatic burden compared with control.

Together, these data demonstrate the flexibility of the B16-F10 model and the importance of aligning implantation route, treatment timing and endpoints with the specific biological and therapeutic question being investigated.

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Researchers at Oncodesign Services compared two approaches for modelling metastatic prostate cancer in immunodeficient male mice. 22Rv1-Luc-mCherry human prostate cancer cells were administered by intra-tibial or intra-arterial injection, with longitudinal bioluminescence imaging used to characterize the timing and anatomical distribution of disease progression.

• Intra-tibial injection: Bioluminescence signals remained localized to the tibia for the first 21 days. From day 28, distant signals became detectable, with ex vivo imaging confirming dissemination to the liver and lungs.

• Intra-arterial injection: Early signals were observed in the bones, followed by increasingly prominent liver involvement. Endpoint imaging also identified signals in the hind-limb bone, spinal column and seminal vesicle.

The two injection routes produced distinct patterns and kinetics of metastatic dissemination. This demonstrates that administration route influences the disease trajectory reproduced by a metastasis model.

In this study, longitudinal imaging provided information that endpoint analysis alone could not capture, including when dissemination became detectable and how metastatic burden developed over time. These data can help inform treatment initiation, cohort allocation and response assessment.

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