Cell fusion segregates progressive growth from metastasis.

Cell fusion has been used to analyse the genetic determinants of metastasis at the cellular level. Highly metastatic mouse melanoma cells were fused with diploid mouse lymphocytes and a range of hybrid clones isolated and tested for tumorigenicity and metastatic potential by s.c. injection into newborn, histocompatible, sublethally-irradiated mice. Although almost all clones tested were tumorigenic, most had considerably reduced metastatic potential. This suggests that tumorigenicity and metastasis are determined by different genetic elements. Histological examination of primary tumours produced by metastatic and non-metastatic hybrid cell lines showed that an essential step in the production of metastases is the separation of tumour cells from the main tumour mass and their movement into the surrounding tissues. The primary tumours of a metastatic hybrid cell line showed local invasiveness whereas those of a non-metastatic cell line did not.