Caki-1 / Caki-1-luc Orthotopic Mouse Model Service for Renal Cancer

The Caki-1 / Caki-1-luc orthotopic mouse model for renal cancer is a VHL wild-type human clear cell renal carcinoma platform in which metastasis-derived Caki-1 cells are engrafted into the kidney of immunodeficient mice, combining organ-faithful tumor histology with hypoxia-driven VEGF biology and spontaneous metastatic competence. Alfa Cytology delivers this model as a complete preclinical capability — covering authenticated Caki-1 / Caki-1-luc expansion and luciferase-stable banking, intrarenal surgical implantation, longitudinal in vivo bioluminescence monitoring of primary and metastatic lesions, and exhaustive histopathological endpoints — all shaped around each sponsor’s therapeutic candidate, dosing strategy, and decision framework.

Overview of Caki-1 / Caki-1-luc Orthotopic Mouse Model for Renal Cancer

Caki-1 is one of the most widely deployed cell lines in renal cancer research, established in 1971 at the Sloan-Kettering Institute by Jørgen Fogh and Germain Trempe from a skin metastasis of a 49-year-old donor with clear cell carcinoma of the kidney. As a line of metastatic origin, it models advanced disease from the outset: it is near-triploid with a modal chromosome count of 68 (range 63–71, no Y chromosome, and 13 marker chromosomes), is TP53 wild-type, and — notably for clear cell biology — retains wild-type VHL while still secreting high levels of VEGF, particularly under hypoxic conditions, a signature ccRCC phenotype. Cultured on permeable supports, Caki-1 cells form a polarized monolayer with apical microvilli and functional characteristics of well-differentiated proximal tubule epithelium, a feature unique among RCC lines. In nude mice the line forms tumors of clear cell histology consistent with the renal primary — both from the bulk population and from side-population fractions — and it grows briskly, with a reported doubling time of about 28 hours.

Fig 1. In vivo BLI of orthotopic Caki-1-luc EV tumors (week 5–6) vs Caki-1-luc A9 (week 4–5) under vehicle or SF+MU, with ROI quantification and H&E of kidney, lung, liver and pancreas metastases. (Jordan, Andre R., et al., 2020)

Orthotopic implantation into the kidney gives this biology its most faithful expression: intrarenal Caki-1-luc tumors develop clear cell morphology in situ, recruit the organ’s vascular niche, and provide a setting in which VEGF-pathway and mTOR-pathway interventions can be interrogated with organ-appropriate pharmacology — documented, for example, by combination and sequential regimens of sunitinib with everolimus in luciferase-transfected orthotopic Caki-1 kidney tumors. Stable firefly luciferase labeling (Caki-1-luc) renders the entire disease course quantitative: engraftment, primary growth, and the emergence of metastatic deposits are tracked longitudinally by in vivo bioluminescence after luciferin administration, with ex vivo organ imaging at necropsy resolving the metastatic map. The platform has likewise been used to dissect hypoxia-linked resistance mechanisms — including sunitinib resistance driven by stanniocalcin 2 and EMT under low oxygen — making Caki-1 / Caki-1-luc orthotopic studies a versatile choice for anti-angiogenic and targeted-therapy evaluation, resistance-biology research, and kidney-function-aware toxicology work.

Cell Line Information: Caki-1 / Caki-1-luc

The table below assembles the defining characteristics of the Caki-1 parental line and its luciferase-labeled derivative Caki-1-luc. Both are human-derived and require immunodeficient hosts for in vivo work.

Our Services

Running a VHL wild-type, histology-faithful orthograft well requires both renal microsurgery skill and disciplined imaging cadence, and Alfa Cytology provides exactly that: authenticated Caki-1 / Caki-1-luc banks, reproducible intrarenal implantation, weekly in vivo bioluminescence schedules, and endpoint pathology — delivered as one accountable preclinical program.

Workflow of Caki-1 / Caki-1-luc Orthotopic Mouse Model Construction

Construction follows established intrarenal xenograft methodology: luciferase-labeled Caki-1 cells are expanded under authenticated conditions, formulated in a Matrigel-supported suspension, implanted beneath the renal capsule or into the renal parenchyma of immunodeficient mice, and followed by serial imaging with histology-confirmed endpoint analysis. The workflow comprises the following stages.

1. Cell authentication and banking: Caki-1 or Caki-1-luc cells are verified by STR profiling, confirmed mycoplasma-free, and expanded into low-passage working banks under standardized McCoy’s 5a culture conditions.
2. Cell harvest and formulation: Healthy adherent cultures are trypsinized, washed, counted and viability-checked, then resuspended at the study-specified dose in the range of 1–5 × 10⁶ cells in 20–30 μL of serum-free medium mixed 1:1 with cold Matrigel and kept on ice until implantation.
3. Anesthesia and renal exposure: Male immunodeficient mice are anesthetized with isoflurane; a left flank incision opens the retroperitoneal space, and the left kidney is gently exteriorized through a warm saline-moistened window.
4. Intrarenal implantation: The cell suspension is slowly injected beneath the renal capsule or into the renal parenchyma of the left kidney; the needle is retained briefly after injection so the Matrigel partially sets, limiting reflux and equalizing take rates across cohorts.
5. Closure and perioperative care: The kidney is repositioned, muscle and skin are sutured in layers, and animals receive analgesia with close post-operative monitoring until fully recovered.
6. Engraftment confirmation and serial imaging: Luciferin is administered intraperitoneally and bioluminescence is acquired to confirm renal tumor take and normalize group allocation; imaging repeats on a weekly cadence to track primary growth and flag emerging metastatic signal.
7. Intervention and endpoint analysis: Experimental arms — sunitinib, sorafenib, everolimus, 5-fluorouracil combinations, anti-angiogenic agents, and sequential regimens — proceed per study design; endpoints integrate imaging with tumor-bearing kidney weight, ex vivo organ bioluminescence, and histopathology (H&E confirming clear cell morphology, plus CD31, Ki67, and marker-specific immunohistochemistry).

Fig 2. Caki-1 / Caki-1-luc orthotopic mouse model construction workflow.

Case Study-Caki-1 / Caki-1-luc Orthotopic Mouse Model Development

Alfa Cytology has executed preclinical programs on the Caki-1 / Caki-1-luc orthotopic platform spanning targeted-therapy and combination-regimen evaluation, hypoxia-linked resistance investigation, and anti-angiogenesis research. In these studies, intrarenally implanted Caki-1-luc tumors were quantified longitudinally by in vivo bioluminescence, with clear cell histology and metastatic distribution confirmed at endpoint by histopathology and ex vivo organ imaging. Study-level data are available on request.

Why Choose Alfa Cytology?

Alfa Cytology unites renal-orthograft surgical expertise with quantitative imaging and histopathology under one roof, so every Caki-1 / Caki-1-luc orthotopic study is executed with reproducible technique and reporting quality sponsors can rely on.

• Focused experience with clear cell renal carcinoma xenografts, including VHL wild-type biology and hypoxia-driven VEGF readouts.
• A single integrated team managing cell banking, kidney implantation surgery, in vivo imaging, and endpoint pathology under one quality framework.
• Longitudinal bioluminescence monitoring covering primary renal growth and early metastatic emergence.
• Flexible regimens spanning VEGF, mTOR, and anti-angiogenic interventions in combination or sequence.
• Transparent milestone reporting and rapid scientific feedback throughout the engagement.

Contact Us

Looking for a histology-faithful, bioluminescent orthotopic platform for your renal cancer program? Alfa Cytology is ready to support you. Reach out to us with your study objectives and endpoint requirements, or contact us today for a customized proposal and quotation for the Caki-1 / Caki-1-luc orthotopic mouse model service.

For research use only. Not intended for any clinical use.