METASTASTIC VARIANTS DERIVED FOLLOWING IN-VIVO TUMOR PROGRESSION OF AN IN-VITRO TRANSFORMED SQUAMOUS-CELL CARCINOMA LINE ACQUIRE A DIFFERENTIAL GROWTH ADVANTAGE REQUIRING TUMOR-HOST INTERACTION

The purpose of this study was to develop an experimental model of squa mous cell carcinoma that can be used to identify molecular and immunol ogic changes associated with primary events in malignant transformatio n, and those associated with metastatic tumor progression in the prese nce of host homeostatic and immunologic factors, Metastatic variants w ere derived following in vivo tumor progression of the in vitro transf ormed squamous cell carcinoma line Pam 212, The parental and metastati c cell lines exhibited similar morphologic features and molecular mark ers of an epithelial lineage, including an epithelial morphology in cu lture, cell surface expression of integrin alpha 6 beta 4, and express ion of mRNA of cytokeratins K6 and K14, When the growth and metastatic phenotype of the parental and reisolate cell lines was compared, the reisolate cell lines were found to exhibit a greater rate of growth an d incidence of metastasis than the parental cell line when reimplanted in vivo, The difference in the growth rate of the parental cell line and the variants observed in vivo was not detected when growth of thes e lines was compared in vitro, suggesting that the growth advantage an d selection of these variants requires tumor-host interaction, The met astatic variants exhibited a similar growth advantage in normal immuno competent and SCID Balb/c mice, indicating that the growth advantage i n vivo is not due to T or B lymphocyte-dependent immune factor(s), We conclude that metastatic variants derived following in vivo tumor prog ression of an in vitro transformed squamous cell carcinoma line exhibi t a differential growth advantage in vivo that requires the host envir onment, Comparison of these in vitro transformed and in vivo derived m etastatic variant cell lines with phenotypic differences in growth and metastasis should prove useful for dissecting the role of tumor and h ost factor(s) in malignant transformation and metastatic tumor progres sion of squamous cell carcinoma.