Tumorigenic suppression of a human cutaneous squamous cell carcinoma cell line in the nude mouse skin graft assay.
The development of human squamous cell carcinomas has been associated with a number of genetic alterations involving chromosome 11, including cytogenetic and allelic deletions as well as amplification of genes in the 11q13 region. To determine the relevance of chromosome 11 in the formation of tumors of stratified squamous epithelial origin, we have introduced, via microcell fusion, a normal human chromosome 11 into the cutaneous squamous cell carcinoma cell line A3886TGc2. The ability of chromosome 11 to modulate the tumorigenicity of A3886TGc2 was evaluated first by inoculating cells s.c. in nude mice. All hybrids remained tumorigenic but exhibited longer tumor latencies than the parent, a result previously observed by other laboratories. We then tested our epidermally derived hybrids in the more physiologically relevant environment of the nude mouse skin graft system. The tumorigenic phenotype of three of four chromosome 11 hybrids placed into nude mouse skin grafts was completely suppressed. Polymerase chain reaction amplification of DNA from normal skin present at the suppressed graft sites failed to detect the introduced human cells. This information indicates that the normal skin is of mouse origin and suggests that the chromosome 11 microcell hybrids did not differentiate in vivo, but most likely failed to survive. We propose that external environmental factors present at the site of inoculation modulate the tumorigenic potential of these cells.
Conway
K
K
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Morgan
D
D
Phillips
K K
KK
Yuspa
S H
SH
Weissman
B E
BE
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002871:Chromosome Banding; D002880:Chromosomes, Human, Pair 11; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012878:Skin Neoplasms / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured