Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate.
The incidence of melanoma continues to increase at a rapid rate. As for most cancers, it is melanoma metastases, rather than the primary malignancy, that is the principal cause of death. We previously showed that the introduction of a normal copy of chromosome 6 into the metastatic human melanoma cell line C8161 suppresses metastasis at a step subsequent to tumor cells entering the bloodstream. To better define the step(s) in metastasis blocked by the addition of chromosome 6 we engineered cells that constitutively express green fluorescent protein (GFP). When these tagged, chromosome 6 hybrid cells were injected intravenously into athymic mice, grossly detectable metastases did not form. However, fluorescence microscopy revealed micro-metastases (single cells or clusters of <10 cells) in the lungs, suggesting that these cells lodged in the lungs but failed to proliferate. Cells isolated from lung up to 60 days post-injection grew in culture and/or formed tumors when injected into the skin, indicating that they were still viable, but dormant. This result implies that the gene(s) on chromosome 6 interfere specifically with growth regulatory response in the lung, but not in the skin. Thus, the gene(s) responsible for metastasis suppression represents a new class of metastasis inhibitors acting at the final stages of the metastatic cascade--that is, affecting the ability of the cells to survive and proliferate at a specific secondary site.
Goldberg
S F
SF
Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey 17033-2390, USA.
Harms
J F
JF
Quon
K
K
Welch
D R
DR
D000818:Animals; D002455:Cell Division; D002470:Cell Survival; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins; D006801:Humans; D006822:Hybrid Cells / Q000637:transplantation; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008164:Luminescent Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008546:Melanoma, Experimental; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000032:analysis; D012878:Skin Neoplasms / Q000556:secondary; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins