Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic and metastatic potency

This study shows that solitary, dormant human cancer cells, retrieved from metastasis-free organs of animals carrying spontaneously metastatic primary tumors, can reactivate their tumorigenic and metastatic potency. The tumors were produced by MDA-MB-435 CL16 breast cancer cel1s permanently labeled with green fluorescent protein and the neomycin resistance gene. This enabled unequivocal identification of tumor cefls emerging from organ explants cultured in neomycin to eliminate nonneoplastic host cel1s. Rescued ccHs resumed proliferation and generated lines that were tumorigenic and metastatic in fresh animals. All resulting primary and secondary tumors were uniformly labeled. Ceffs recovered from bone marrows and spleens, where there were no metastases, were as tumorigenic and metastatic as ceRs recovered from lungs and lymph nodes, which are the preferred sites of colonization for this tumor line. This evidence that malignant growth of disseminated cancer cells is suspended indefinitely by microenvironmental. conditions in metastasis-free organs, although it is still active in others of the same host, shows that neoplastic progression can be arrested and has far-reaching biological and clinical implications. Specifically, it predicts the existence of natural, nonimmune host mechanisms that stimulate or inactivate tumor growth in different anatomical sites, which may be exploitable for therapeutic benefit.