In Vivo and in Vitro Selection of Experimental Metastatic Variants of Rodent Melanoma, Mammary Carcinoma and Lymphosarcoma

Abstract

Metastasis via lymphatics and blood does not always result in tumor colonization of tissues and organs based strictly on anatomical considerations (Salsbury, 1975; Sugarbaker, 1952). Many blood-borne experimental metastatic tumor systems show nonrandom colonization patterns that do not correlate with the initial capillary beds encountered (Dunn et al., 1954; Parks, 1974; Fidler and Nicolson, 1976, 1977; Brunson and Nicol son, 1978, 1979; Conley, 1979). After their initial arrest, malignant cells may die, invade and grow or detach and recirculate to other sites (Zeidman, 1961; Fisher and Fisher, 1967; Fidler and Nicolson, 1976, 1977; Brunson and Nicolson, 1978, 1979) suggesting that factors other than non-specific trapping in the microcirculation determine secondary site location (Nicol son, 1978). In order to determine the host and tumor cell properties important in metastatic tumor spread and survival at distant sites, we have developed animal tumor models in syngeneic hosts that show distinct metastatic behaviors. Several of these models have been based on sequential selection of murine B16 melanoma lines for enhanced blood-borne implantation, survival and growth to obtain sublines capable of preferentially colonizing lungs (Fidler, 1973), brain (Brunson et al., 1978) or ovary (Brunson and Nicol son, 1979). Similarly we have selected in vivo murine RAW117 lymphosarcoma sublines that show enhanced liver colonization after intravenous (i.v.) administration (Brunson and Nicolson, 1978) and rat 13762 mammary adenocarcinoma sublines that show colonization of regional lymph nodes and/or lungs after implantation subcutaneously (s.c.) (Neri et al., 1979). In addition, it has been possible to select tumor cell variant sublines in vitro for loss of sensitivity to cell-mediated toxicity (Fidler et al., 1976), decreased binding to immobilized-lectins (Reading et al., 1980) and increased invasion of tissues (Hart, 1980) or veins (Poste et al., 1980).