Role of ras Oncogenes in Experimental Models of Metastasis

Abstract

The most important characteristic of malignant tumors is their ability to metastasize. Although some progress has been made in understanding how cancer cells disseminate, the underlying mechanism is still unknown. Primary tumors contain heterogenous cell populations that differ in their metastatic capacity (1, 2). Metastatic and nonmetastatic tumor cell clones have been established from the same primary tumor (3), but so far no genetic elements specific for the metastatic phenotype have been identified. Somatic cell hybridization in vitro has been used extensively to study expression and regulation of the malignant phenotype (4). It has also been used to analyze some of the factors involved in the metastatic process (5, 6). Some reports have appeared on in vivo tumor-tumor cell or tumor-host cell hybridization, which in some instances can lead to an increase in the metastatic potential (4). However, most studies on in vitro hybridization between tumor cells and normal cells have demonstrated that the transformed and the metastatic phenotypes are recessive in nature (7, 8). Cytogenetic analyses have associated higher ploidy and more chromosomal abnormalities with advanced stages of malignancy (9). The acquisition of high chromosome numbers may lead to tumor progression through increased dosage of genes that may be involved in metastasis. Chromosomal changes consistent with gene amplification seen with increased malignancy include: double minutes (10), abnormally banded regions (11), and homogeneously stained regions (12).