A Murine Model for Metastatic Conjunctival Melanoma

Area of Science:

• Ophthalmology
• Oncology
• Translational Medicine

Background:

• Conjunctival melanoma (CM) is an aggressive ocular cancer known for frequent local recurrences and potentially fatal metastases.
• Developing an effective preclinical model is crucial for understanding CM pathogenesis and evaluating novel therapeutic strategies.

Purpose of the Study:

• To establish and characterize a murine model of conjunctival melanoma (CM) for studying tumor growth, metastasis, and therapeutic responses.
• To assess the orthotopic growth and metastatic potential of three distinct human CM cell lines in immunodeficient mice.

Main Methods:

• Human CM cell lines were injected subconjunctivally into NOD/SCID IL2 rγnull mice to establish orthotopic xenografts.
• Primary tumor cells underwent serial in vivo passaging to enhance metastatic capability.
• Melanoma marker expression (HMB-45, S100B, MART-1) and mutational status (BRAF, NRAS) were analyzed in cell lines, xenografts, and metastases.

Main Results:

• All inoculated mice (n=101) developed subconjunctival tumors within 2 weeks, demonstrating robust orthotopic growth.
• Serial in vivo passaging led to the formation of metastases in draining lymph nodes in a subset of mice (n=21).
• Tumors and metastases consistently expressed melanoma markers; genetic analysis revealed BRAF or NRAS mutations in the cell lines and xenografts.

Conclusions:

• A reproducible murine model for conjunctival melanoma (CM) has been successfully established.
• This model exhibits metastatic patterns that closely resemble human CM, making it valuable for preclinical research.
• The model supports in vivo testing of new therapies for conjunctival melanoma.