786-O / 786-O-luc Orthotopic Mouse Model Service for Renal Cancer

The 786-O / 786-O-luc orthotopic mouse model of renal cancer engrafts a VHL-deficient human clear cell renal carcinoma line directly beneath the kidney capsule of immunodeficient hosts, preserving organ-specific stroma, vascularization and the metastatic routes of the human disease. From authenticated cell banking and subcapsular implantation surgery to serial luciferase imaging, primary tumor excision and lung metastasis staging, Alfa Cytology delivers complete 786-O / 786-O-luc orthotopic programs engineered around each sponsor’s target, regimen and decision point—strictly as preclinical research.

Overview of 786-O / 786-O-luc Orthotopic Mouse Model for Renal Cancer

O is one of the oldest and most widely used human renal cancer cell lines, established in 1976 from a primary clear cell adenocarcinoma of the kidney removed from a 58-year-old male patient. Its defining molecular feature is a truncating mutation in the von Hippel-Lindau (VHL) tumor suppressor gene: loss of pVHL locks hypoxia-inducible signaling in the “on” state, and because the cells lack HIF-1α the entire hypoxic program—including high-level VEGF and carbonic anhydrase IX—is executed by HIF-2α alone. This configuration mirrors the dominant molecular lesion of human clear cell renal cell carcinoma and has made 786-O the reference line for VHL/HIF-pathway research, from the classic demonstration that restoring wild-type VHL abolishes tumorigenicity in vivo to the modern era of HIF-2α inhibitors.

Fig 1. Orthotopic implantation of OSRC-2 cells with PT2399/vehicle oral gavage: body weight change, tumor weight, HIF-2α/Cyclin D1/NDRG1 westerns, and iWAT/eWAT wasting analysis in the 786-O/OSRC-2 cachexia model. (Abu-Remaileh, Muhannad, et al., 2026)

Because 786-O is a human line, orthotopic modeling requires immunocompromised recipients such as athymic nude or NSG mice. Implanted under the renal capsule, the cells vascularize within authentic kidney stroma and grow into primary tumors that can shed metastases to the lung and, less commonly, the liver, while also supporting experimental metastasis formats such as tail-vein and bone-seeding assays. The luciferase-tagged 786-O-luc variant adds quantitative, non-invasive bioluminescence readouts—detectable within days of implantation after D-luciferin administration—that track primary tumor burden longitudinally and flag pulmonary lesions before they are palpable; reporter behavior is validated in vitro by luminometer before any animal work begins. One caveat researchers should weigh is that long-term culture has driven partial dedifferentiation, so xenograft histology can appear sarcomatoid rather than classically clear-cell; even so, the model remains a standard-bearing preclinical tool for targeted therapy, anti-angiogenic, HIF-2α, CAIX/radiation-response and metastasis studies.

Cell Line Information: 786-O / 786-O-luc

786-O and its luciferase-labeled derivative 786-O-luc originate from the same human clear cell adenocarcinoma; the reporter line additionally carries a stable firefly luciferase cassette for optical imaging without altering tumorigenic behavior in vitro or in vivo. Key characteristics are summarized below.

Our Services

Drawing on hands-on in vivo oncology expertise and in-house imaging, surgical and pathology capabilities, Alfa Cytology tailors each 786-O / 786-O-luc orthotopic engagement to the sponsor’s scientific question—calibrating cell dose, Matrigel ratio, implantation lobe, dosing onset and endpoint panels to deliver clean, decision-grade preclinical data.

Workflow of 786-O / 786-O-luc Orthotopic Mouse Model Construction

Orthotopic construction of the 786-O / 786-O-luc model is a survival-surgery workflow conducted under inhalation anesthesia with aseptic technique, scheduled analgesia and daily post-operative welfare checks consistent with institutional animal-care standards. A typical study proceeds through the following stages:

1. Cell line qualification: 786-O or 786-O-luc vials are mycoplasma-tested and STR-verified; luciferase-positive cells are confirmed in vitro by luminometer to express uniform, stable signal before expansion.
2. Animal preparation: immunodeficient mice (athymic BALB/c nude or NSG, typically 4–8 weeks old) are acclimatized, health-screened and randomized by body weight ahead of surgery.
3. Anesthesia and asepsis: mice are anesthetized with isoflurane, the flank is clipped and disinfected, and a sterile field with sterile instruments is maintained throughout.
4. Surgical exposure: a small flank incision opens the abdominal wall, and the kidney is gently exteriorized onto sterile gauze to present the renal capsule under magnification.
5. Subcapsular inoculation: 786-O / 786-O-luc cells (commonly 1 × 10⁶ in 20–50 µL PBS, often mixed 1:1 with 50% Matrigel) are injected beneath the renal capsule with a fine needle, forming a controlled subcapsular bleb.
6. Repositioning, closure and analgesia: the kidney is returned to the abdomen, muscle and skin are closed with absorbable sutures and wound clips, and buprenorphine or meloxicam is dosed on schedule until full recovery.
7. Longitudinal monitoring: primary tumor growth is tracked in vivo by weekly bioluminescence imaging after intraperitoneal D-luciferin (~150 mg/kg) for 786-O-luc, supplemented by body-weight measurements and clinical scoring; ultrasound or MRI can be added for anatomical confirmation.
8. Endpoint and analysis: at termination the tumor-bearing kidney is excised and tumor mass determined by subtracting the contralateral kidney weight, tumor dimensions are recorded, lungs and liver are inspected with ex vivo bioluminescence and histology for metastasis, and tissues are processed for IHC, molecular assays and downstream profiling.

Fig 2. 786-O / 786-O-luc orthotopic mouse model construction workflow.

Case Study-786-O / 786-O-luc Orthotopic Mouse Model Development

Alfa Cytology maintains an expanding preclinical case-study collection for the 786-O / 786-O-luc orthotopic platform, covering establishment-phase optimization of cell dose and implantation technique, serial bioluminescence tracking of primary renal tumors in vivo, targeted-therapy and HIF-pathway intervention studies, and systematic lung metastasis evaluation with matched histological confirmation. Illustrative materials—including imaging series, tumor growth trajectories and endpoint summaries—are available on request and are refreshed as additional programs conclude.

Why Choose Alfa Cytology?

Teams select Alfa Cytology for this model because every phase—from cells to surgery to imaging to endpoints—is executed with model-specific discipline:

• A practiced orthotopic surgery group delivering fast, high-survival subcapsular implantation.
• STR-verified 786-O and stably luciferase-labeled 786-O-luc banks ready for immediate mobilization.
• Quantitative bioluminescence that supports signal-based randomization and within-animal longitudinal readouts.
• Authentic kidney-context tumor growth with spontaneous lung metastasis relevant to human clear cell renal carcinoma.
• A configurable endpoint menu spanning efficacy, metastasis staging, histopathology, IHC and molecular analysis.
• Experience with diverse treatment modalities, from HIF-2α inhibitors and TKIs to radiation and oncolytic agents.
• Direct, single-point project communication with milestone-based progress reporting.
• An exclusively preclinical mandate, with all studies designed, conducted and reported as non-clinical research.

Contact Us

If the 786-O / 786-O-luc orthotopic renal cancer model matches your next preclinical objective, contact us to share your target, timeline and desired endpoints. The Alfa Cytology team will reply with a customized plan covering model setup, imaging cadence and analysis strategy—reach out today and take the next step with confidence.

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