The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1 alpha, IL-6, GM-CSF, and KC

Human and murine squamous cell carcinomas (SCC) have been reported to produ ce proinflammatory cytokines IL-1 alpha, IL-6, GM-CSF, and IL-8 or KC. Prod uction of individual members of the proinflammatory cytokine family has bee n associated with increased tumor growth or metastasis in a variety of neop lasms. In this study, we determined whether the expression of these cytokin es occurs as a result of the events of cellular transformation or culture, or is promoted by interaction of neoplastic cells with factors or cells in the host environment. We compared the expression of proinflammatory cytokin es following the spontaneous transformation of murine keratinocytes in vitr o, and following the formation of tumors and metastases from these transfor med keratinocytes in syngeneic recipients in vivo. Using sensitive ELISA as says, we found that cultures of the in vitro transformed Balb/c SCC line Pa m 212 do not produce elevated levels of proinflammatory cytokines IL-1 alph a, IL-6, GM-CSF and KC, indicating that transformation or culture alone is insufficient to account for the level of cytokine expression detected in pa tient and experimental tumors. In contrast, Pam reisolates from primary and metastatic tumors were obtained which constitutively produce markedly elev ated levels of cytokines IL-1 alpha, IL-6, KC and GM-CSF. The increase in t he expression of these cytokines by SCC in vivo occurred independent of T a nd B lymphocyte-mediated immunity, since increases in expression of the cyt okines was observed in lines reisolated from immunodeficient athymic nude a nd SCID Balb/c congenic mice. The increased expression of cytokines appeare d to result from additional events in vivo, rather than due to selection of a pre-existing cytokine-producing subpopulation, since clones of the paren tal cell line expressed lower cytokine levels than cloned reisolates, and c lones of the non-secreting parental cell line that formed tumors in vive se creted elevated levels of cytokines following reisolation. We conclude that the development of SCC that express proinflammatory cytokines is promoted by tumor-host interaction(s) that are independent of specific T and B cell immunity.