Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes

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.