Abstract
Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co-localisation and co-growth in nude mice by taking advantage of the sensitivity of the histochemical marker genes for localising them. After intravenous co-injection of equal numbers of both cells to analyse experimental metastasis, most foci transiently established in the lung for several hours were comprised of only one cell class. However, a significant fraction of foci contained both cell types, as identified in double-stained whole-lung tissues and in lung sections. Evidence was obtained that LZEJ cells increase the survivability and subsequent growth of APSI-containing micrometastases during co-localisation in lung, when compared to APSI cells injected alone. Conversely, APSI cells facilitate expansion of LZEJ cells from micrometastatic foci into overt-metastatic nodules in the lung. These analyses reveal reciprocity during experimental metastasis by two related tumour cell classes derived from the same parental cell.