Orthotopic Tumor Model Studies

Orthotopic models involve the seeding of tumor cell lines or patient-derived cell xenografts into animal models. This strategy allows us to assess tumor development in a relevant environment and evaluate efficacy in a preclinical tumor model that mimics the disease process in humans. With orthotopic models, we can closely monitor and accurately quantify primary tumor growth, metastatic activity, and response to therapy scenarios.

Charles River offers orthotopic models across a full range of tumor histotypes to provide the most disease-relevant tumor environment in which to test your drug.

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We can evaluate disease progression through a variety of methods, including clinical signs, survival study design, and our imaging platform that has both in vivo and ex vivo capabilities:

  • High-throughput or high-resolution imaging
  • Real-time in-life fluorescence and bioluminescence imaging (IVIS)
  • 3D optical tomographic reconstructions for both bioluminescence and fluorescence
  • µCT X-ray for anatomical reference of signal

With human disease-specific tumor microenvironments and in-life imaging, Charles River’s orthotopic models are ideal for elucidating mode of action, monitoring patient-relevant responses, and targeting metastatic mechanisms.

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In orthotopic models, tumors are implanted into the equivalent organ from which the cancer originated to mimic human disease.

Figure 1: Diagram of Orthotopic Tumor Model

Micropathology of breast tumor model, to represent the tumor models available in Charles River’s Cancer Model Database.

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Charles River's Orthotopic Models

  • Ascites Model of Solid Cancer

    Different cancer cell lines, such as ovarian cancer cell line A2780-luc or OVXF 1023-iRFP, are injected intraperitoneally to mimic the clinical symptoms of cancer-induced ascites. Tumor load is monitored by optical imaging.

    Available Cell Lines

    • Human - OVF1023
  • Bladder Model of Cancer

    Bladder cancer cell lines, such as MBT2 iRFP, are directly implanted into the bladder layer in C3H/He mice. Effect of test agents is evaluated using optical imaging

    Available Cell Lines

    • Murine - MBT2
  • Breast Cancer Models

    Cancer lines such as BT474 can be injected directly into the mammary fat pad of the mouse in this orthotopic tumor model of cancer.

    Available Cell Lines

    • Human - MCF-7, SK-BR-3, MDA-MB231,
    • Murine - 4T1-luc
  • Colon Cancer Models

    Available Cell Lines

    • Human - 269, 1103, Caco-2, COLO 205, Difi, DLD-1, HCC-2998, HCT 116, HT-29, KM12, KM20L2, LS-174T, RKO, SW480, SW620
    • Murine - CT26, MC38
  • Intracranial Orthotopic Model

    Intracranial injection of tumor cells, such as CMV U87MG human glioma cells, mimics tumor growth in the brain environment. Test agent effects are evaluated based on optical imaging and scoring of neurological observations.

    Available Cell Lines

    • Human - U87MG

    Example data: Intracranial U87MG orthotopic model

    Intracranial U87MG orthotopic tumor model with ex vivo intracranial imaging at day 65. Luminescence is quantified to measure tumor progression and effect of test compound.

    Intracranial U87MG tumor model, with ex vivo intracranial imaging at Day 65.

  • Intrasplenic Hepatic Colonization Model

    Orthotopic seeding of human tumor cell lines, such as HT29 and HT29-luc2, allows assessment of tumor development in a hepatic environment and provides efficacy evaluation in a preclinical tumor model mimicking the disease process in humans. This allows for a more representative picture of tumor growth and response to therapy scenario to be realized.

    Available Cell Lines

    • Human - SK-HEP-1
  • Lung Cancer Models

    Lung cancer cell lines, such as SHP-77, and NCI-H292 iRFP, are directly implanted into the lung tissue. Effect of test agents is evaluated using optical imaging.

    Available Cell Lines - Small-Cell Lung Cancer (SCLC)

    • Human - SHP-77

    Available Cell Lines - Non-Small-Cell Lung Cancer (NSCLC)

    • Human - H292
  • Metastatic Model of Solid Cancer

    Different cancer cell lines, such as B16F10, from solid cancer are injected intravenously to mimic the metastatic process. Tumor load is monitored by optical imaging and/or flow cytometry on peripheral blood draws.

  • Ovarian Cancer Models

    Ovarian cancer cell lines (e.g., A2780-luc) are implanted into the mouse models.

    Available Cell Lines

    • Human - OVCAR-3, A2780, OVXF 1023, SKOV-3
  • Pancreatic Models

    Pancreatic tumor cell lines (e.g., MiaPaCa-2, Panc02) are implanted into the mouse pancreas.

    Available Cell Lines

    • Human - Panc02, MiaPaCa-2
  • Prostate Orthotopic Models

    Prostate cancer cell lines (e.g., PC3, LNCAP, DU145) are implanted into the prostate tissue of the mouse model.

    Available Cell Lines

    • Human - PC-3, PC3M, DU145
    3D renderings of prostate cancer orthotopic models

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  • Renal Sub-Capsule Orthotopic Model of Cancer

    The renal orthotopic tumor model was developed for the efficacy evaluation of novel anticancer compounds using a tumor growth delay model that mimics the disease process in humans. Cell lines used in this tumor model include 786-O.

  • Skin Cancer Models

    Available Cell Lines - Melanoma

    • Human - A375
    • Murine - B16F10
  • Systemic Leukemia/Lymphoma/Multiple Myeloma Tumor Models

    In this disseminated orthotopic tumor model, hematological cell lines are injected, such as Raji-B, Granta-519, or Ramos, either intravenously, intrasplenic, or intratibial. Tumor load is monitored by optical imaging and flow cytometry on peripheral blood and clinical observations.

    Available Cell Lines - Leukemia

    • Human - ARH-77, CCRF-CEM, HEL92.1.7, HL-60, K562-CD19, Kasumi-1, KG-1, KG-1a, MEC-1, MEG-01, MOLM-13, MOLT-4, MV4-11, NALM-6, NOMO-1, OCI-AML2, OCI-AML3, RS4;11, THP-1

    Available Cell Lines - Lymphoma

    • Human - Granta-519, JURKAT, K-562, Mino, Namalwa, RajiB, RL, U937
    • Murine - A20, L1210

    Available Cell Lines - Multiple Myeloma

    • Human - H929, L-363, MM.1R, MM.1S, RPMI-8226, U266
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Combining our range of tumor models with quantifiable imaging data creates a truly translational platform in which to test your compounds. Charles River's expanding collection of luciferase transduced tumor cell lines and orthotopic Imaging models are key tools for evaluating the activity of cellular therapies in hematological and solid tumors.

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Frequently Asked Questions (FAQs) About Orthotopic Models

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