CORRELATION BETWEEN CELL-DIFFERENTIATION STAGE, TYPES OF INVASION, AND HEMATOGENOUS METASTASIS IN EXPERIMENTAL RHABDOMYOSARCOMAS

Cancer malignancy is directly related to invasiveness and metastasis a nd inversely related to the degree of tumor differentiation. The relat ion between the stage of cell differentiation and the types of invasio n leading to metastasis is not entirely clear. Intramuscularly transpl anted rat rhabdomyosarcomas are good models to study cell differentiat ion, invasion, and metastasis. Rat rhabdomyosarcoma cell lines (SMF-Ai , SMF-Da, and RMS-B and its clones) with defined invasive and metastat ic potentials have been established. The stage of myogenic differentia tion was evaluated morphologically and by immunohistochemistry. Invasi veness was evaluated according to the infiltration of muscle fibers an d basal lamina. The SMF-Ai line is highly invasive and metastatic. It is composed of premyoblasts that were involved in intercellular, trans laminar, and transcellular invasion of muscle fibers. The SMF-Da line is noninvasive and nonmetastatic. It is composed of myoblasts. The RMS -B line and its clones were at different stages of differentiation and they differed in their invasiveness and metastatic potentials. In hig hly invasive and metastatic clones (RMS-Bg and RMS-Bc), premyoblasts w ere involved in translaminar invasion. Clones composed of myoblasts, r habdomyoblasts, and myotubes only showing intercellular invasion did n ot present hematogenous metastasis. Our results demonstrate a correlat ion between premyoblastic stage of differentiation and translaminar in vasion. The presence of translaminar invasion is directly related to h ematogenous metastatic ability of rat rhabdomyosarcomas. (C) 1995 Acad emic Press, Inc.