Influence of epithelio‐mesenchymal interactions on tumor induction by polyoma virus

Submandibular salivary glands (strain C3H/Bi mice), at stages of development ranging from prerudimentary condition through full development, were tested for their capacity to give rise to tumors after infection with polyoma virus (PV). Responsiveness was judged on the basis of (1) morphologic transformation in organotypic culture, and (2) the development of tumors within PV‐infected transplants to syngeneic newborn hosts. By the tumor‐in‐transplant criterion, the salivary gland was susceptible to the oncogenic action of PV from rudiment Stages 2 and 3 (11% incidence) through higher stages including complete development. With rudiments or glands beyond Stage 4, tumors developed in 60 to 78% of the infected transplants. No tumors developed from Stage 1 or from prerudimentary tissues. It is evident that in this organ, capacity of neoplastic response to PV develops concurrently with morphogenesis and does not diminish with advanced organ development. Morphologic transformation was seen in organotypic cultures of infected glands and rudiments of all stages, including Stage 1. However, the precise origin and the biologic capacities of the transformed epithelium in Stage 1 cultures remain in question. When Stage 2 to 5 rudiments were separated into epithelial and mesenchymal components by trypsinization, neither component alone gave rise to tumors after PV infection and transplantation to newborn recipients. Recombination of the infected components before transplantation restored the capacity to develop neoplasia (23% incidence). These results suggest that, in mouse salivary glands, the unit responding neoplastically to PV is an epithelio‐mesenchymal complex. It is postulated that the integrity of this complex is a critical factor in: (1) conditioning salivary gland epithelium to the initiating action of PV; (2) promoting the emergence of tumor; and (3) directing the pattern of tumor growth.