Studies on relationships between metastatic and non-metastatic tumor cell populations using lineages labeled with...

The relationships between metastatic and non-metastatic cell populations co-existing in composite neoplasms have been studied using cell lineages marked with a dominant selectable marker (neomycin resistance), by transfection. The experimental circumstances were arranged so that the lineages were known to be genotypically distinct (i.e. not merely phenotypic variants of the same lineage) and so that a single metastatic clone was each time combined with a mixed polyclonal non-metastatic population and both partners were distinctly and recognizably marked. This made it possible to ascertain the fates of clones with different metastatic capabilities during tumor progression and metastasis and evaluate their relative contributions to the clinical extent of disease. It was found that metastatic and non-metastatic cell lineages co-existed in most of the late-stage primary tumors examined and that a cell lineage that is invariably non-metastatic, when growing on its own, can with surprising frequency be found thriving in distant metastatic deposits, when it grows to form a primary tumor in combination with a metastatic partner. In fact, occasional metastases from such tumors contained no detectable cells of the metastatic lineage. The endowment of a tumor cell lineage with a new, clinically significant, capability which it convincingly and reproducibly did not manifest before, by another coexisting cell population raises several new questions about the contribution of such phenomena to the overall debilitating properties of the neoplasm and the geometric progression of its impact on the host.