Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice.
The pigment epithelium of the retina (RPE) is derived from the optic cup and is essential for function and development of the eye. We produced a transgenic mouse line that expresses simian virus (SV40) transforming sequences under control of the 1.4 kb tyrosinase-related protein 1 (TRP-1) promoter, targeting expression of T antigen (Tag) to the RPE. In transgenic embryos, RPE cells proliferated in the anterior part of the eye and near the optic nerve. This resulted in formation of tumors, which were pigmented and of epithelial origin. In 3 months-old mice, pigmented cells were detected in spleen and inguinal lymph nodes. In spleen, tyrosinase, TRP-1 and SV40 Tag were expressed and tyrosinase was enzymatically active. Pigmented regions were positive for an epithelial marker, cytokeratin. Cell lines were established from tumor and metastases and kept in culture for more than 2 months. These were pigmented, and maintained expression of tyrosinase, TRP-1, cytokeratin and SV40 Tag. This demonstrates that RPE tumor cells metastasize to lymph node and spleen. In conclusion, the metastasis from TRP-1/Tag RPE tumors towards spleen and lymph nodes serves as potential tool to investigate biology and metastasis of tumors derived from the pigment epithelium.
Penna
D
D
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Schmidt
A
A
Beermann
F
F
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004847:Epithelial Cells / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006119:Groin; D008207:Lymphatic Metastasis; D008543:Melanins / Q000096:biosynthesis; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009928:Organ Specificity; D010088:Oxidoreductases; D010857:Pigment Epithelium of Eye / Q000196:embryology / Q000473:pathology*; D010858:Pigmentation; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019572:Retinal Neoplasms / Q000209:etiology / Q000473:pathology*; D013539:Simian virus 40 / Q000235:genetics; D013160:Splenic Neoplasms / Q000473:pathology*
D000952:Antigens, Polyomavirus Transforming; D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1