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The test models
In contrast to subcutaneously engrafted cells, cells proliferating inside the organ of their origin (‘orthotopically’) spread to metastatic sites in other organs, with specificities comparable to the human situation. Besides allowing the cells to spread, the organotypical stromal interactions that are allowed to occur in such orthotopic models have also been shown to affect the growth, differentiation, and drug sensitivity of tumor cells.
In order to detect the orthotopically implanted cells, a luciferase expressing cell pool has been generated via transduction of a luciferase-neomycin construct and subsequent neomycin selection.
After surgery, the growth of the cells may be monitored via in vivo bioluminescence imaging. The animals are randomized into treatment groups according to apparent tumor sizes. Moreover, once treatment is initiated, effects on the total in vivo bioluminescence signal, and thus primary tumor and potential metastatic loci may be monitored.
At necropsy the tumors, as well as potentially metastatic organs, are homogenized, and the luciferase activity is assayed as a proxy for spread tumor cells. The pattern of metastatic spread is cell type specific for the different models. |
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RENCA-LN tumor in the kidney, cytokeratin-18-stained
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Mice orthotopically implanted with PC-3-LN tumors
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| Tissue Origin |
Tumor Cell Line |
Species |
Fact
Sheet |
| Blood / Leukemia |
MOLM-13 |
Human |
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MV4-11 |
Human |
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| Breast |
MDA-MB-231 |
Human |
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MDA-MB-231
Metastasising Model |
Human |
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| Kidney |
RENCA |
Mouse |
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Pancreas |
AsPC1 |
Human |
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MiA-PaCa2 |
Human |
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| Prostate |
PC-3 |
Human |
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LNCaP |
Human |
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Study example
In the example showed here, mice bearing orthotopically implanted RENCA-LN tumors were treated with Sorafenib or Sutent.
Tumor growth was monitored using biolumines-cence (upper panel). Tumor sizes were determined via in vitro bioluminescence (lower panel, dark colours) or calipering (lower panel, light colours).
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Study example with RENCA-LN tumors implanted orthotopically, and treated with Sorafenib (blue),
Sutent (green), or vehicle (red), respectively
[click here to enlarge image]
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Our service
Base package
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Culturing of the required cell line
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Orthotopic implantation of tumor cells including complete surgery
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Measurements of animal weight, tumor weight (at necropsy), tumor volume (once weekly in vivo via bioluminescence imaging, and at necropsy by callipering)
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Administration of test compound (e.g. p.o., i.p., s.c., i.v.) for approx. 21 days
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Blood sampling
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Ex vivo Luciferase assay of metastases pattern in selected organs (max. 5)
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Shipment of harvested tumor tissues and selected organs
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Preparation of detailed report
Optional
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Fixation of tissues using different fixation agents
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Paraffin embedding of collected tissues using an automated system (Leica TP 1020 and
Leica EG 1160)
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Histological sectioning of paraffin-embedded (Leica SM 2000R) or cryoconserved tissues (Leica CM 3050)
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Hematoxylin-Eosin staining of tissue slides for histological analysis
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Selected immunohistochemistry analysis
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Custom-tailored composition of tumor tissues of an entire in vivo study to a single “Tissue Microarray” for further analysis
Please inquire to receive a custom-tailored quote according to your individual requirements.
Summary fact sheet
ProQinase's service portfolio of orthotopic tumor models
Related Products and Services:
Subcutaneous Tumor Models (Xenografts)
In Vivo Angiogenesis Assay
Tissue Microarray (TMA)
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