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Newt Squamous Carcinoma Proves Phylogenetic Conservation of Tumors as Caricatures of Tissue Renewal¹

Division of Pharmacology and Toxicology, Hipple Cancer Research Center, 4100 South Kettering Blvd., Dayton, OH 45439-2092 [N. P. Z., R. E. P.], and Laboratory of Molecular Biology, Department of Biology, University of Dayton, Dayton, OH 45469-2320 [P. A. T., K. D. R-T.]

Although regeneration-competent newts like Notophthalmus viridescens have been reported to be resistant to carcinogenesis, we have been able to induce transplantable epidermal squamous cell carcinomas with 10–20% incidence by implanting 20-methylcholanthrene s.c. into the scapular region, a tissue that cannot regenerate. As soon as 1 week after exposure to this carcinogen, malignant cells were present in the treated skin, and after 4 weeks, macroscopic tumors of infiltrating squamous carcinoma cells positive for Type IV collagenase and/or ras^Ha p21 had dissolved areas of the epidermal basement membrane and colonized the dermis. Analysis of Ki-67 expression revealed that these tumors grow via a high growth fraction rather than a short cell cycle time. Morphological and immunohistochemical analyses showed that these tumors caricature the biology of the renewing epidermis: the presence of basal-like cells; differentiating cells; apoptotic cells; and keratinized horn pearls with an exaggerated or overabundant stem cell compartment as compared to the differentiated cell compartment. Immunochemical analyses indicated that the squamous carcinomas arose from the epidermis rather than the mucous glands. Thus, the principle that malignant tumors caricature the process of tissue renewal originally established in rodent tumors appears to be valid down the phylogenetic tree at least to regeneration-competent amphibia. Such a broad conservation indicates that the caricature principle also holds in human tumors.

¹ Supported in part by Grant CA51325 from the National Cancer Institute; by benefactors of the Hipple Cancer Research Center such as the Dayton Exchange Club, the Phi Beta Psi Sorority, the Moraine Lyceum Society, and Kettering Fairmont High School; and by the Research Institute of the University of Dayton. The Developmental Studies Hybridoma Bank is maintained by a contract from the NICHD (NO1-HD-2-3144).

² To whom requests for reprints should be addressed, at Mod-1, Rm 2023, ORR, CDER, FDA, 8301 Muirkirk Road, Laurel, MD 20708.

Received 12/ 5/91. Accepted 7/ 7/92.