The use of cell fusion to analyse factors involved in tumour cell metastasis

Abstract

Cell fusion has been used to study some of the factors involved in the process of metastasis. Highly metastatic rat mammary adenocarcinoma cells were fused with various non-metastatic cells and the hybrid clones isolated. These were then tested for their metastatic potential either by injecting the cells intravenously and measuring lung colony formation or by injecting the cells subcutaneously and measuring their ability to form lymphatic metastases. With most hybrid clones tested, the metastatic potential was either inhibited or greatly suppressed; thus this phenotype is a recessive characteristic. We also monitored the hybrid cells' ability to produce plasminogen activator (PA) a serine proteinase thought to be involved in the formation of metastatic lung foci. Whilst the highly metastatic parent cells produced large quantities of PA, none could be detected in the non-metastatic lines. Although the hybrid clones produced little PA activity this could not be correlated with their decreased metastatic potential in that one clone, after extensive in vitro culture, reverted to a more metastatic line without a concomitant increase in PA activity. The suppressed PA activity may be due to the presence of an inhibitor that is spontaneously produced by the hybrid cells.

KAI1 , a Metastasis Suppressor Gene for Prostate Cancer on Human Chromosome 11p11.2

“…Both positive and negative regulators of metastasis are likely to exist. The existence of genes involved in metastasis suppression is suggested by somatic cell genetic studies in which nonmetastatic and metastatic tumor cells are hybridized and the resultant cell hybrids are tumorigenic but no longer metastatic (2). For example, the metastatic ability of rat AT6.1 prostate cancer cells was suppressed when they were fused to nonmetastatic cancer cells (3), and the putative metastasis suppressor gene was mapped to human chromosome llpll.2-13 (the pl1.2-13 region of chromosome 11) by microcell-mediated chromosome transfer (4).…”

Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression

“…Evidence for the genetic control or modulation of metastasis was generated from a number of studies, utilizing somatic cell hybrid fusions between non-metastatic and metastatic tumor cells (Miele et al, 1996;Ramshaw et al, 1983;Welch et al, 1994). The resulting hybrids, while retaining their tumorigenic potential, were unable to metastasize.…”

Genetic factors and suppression of metastatic ability of v-Ha-ras-transfected rat mammary cancer cells.

“…Alternatively, these results suggest that the suppression of high metastatic ability in hybrid clones is due to the replacement of the expression of a metastasis suppressor gene(s) provided by the nonmetastatic parental clone. Indirect evidence for the existence of a metastasis suppressor gene(s) has also been demonstrated by several cell fusion studies (20)(21)(22)(23)(24). In these studies, metastatic potential was suppressed when rat metastatic mammary carcinoma cells were fused with various nonmetastatic cells (20), when mouse metastatic melanoma cells were fused with normal cells (21,22), when mouse metastatic lung carcinoma cells were fused with tumorigenic but nonmetastatic mouse L cells (23), and when highly metastatic rat prostate cancer cells were fused with nonmetastatic rat prostate cancer cells (24).…”