Spontaneous metastatic potential of rat hepatocarcinoma cells after cell fusion or DNA transfection.
Eight LF x ICIG cell hybrid clones, isolated upon fusion of normal ICIG-7 human fibroblasts with tumorigenic, non-metastatic LF Cl.2A cells derived from a DAB-induced rat hepatocarcinoma, were studied. They were all highly tumorigenic and were capable of developing spontaneous lung metastases in syngeneic animals. All the hybrids were characterized by a rapid loss of human chromosomes. However, in long-term culture, they all revealed a persistence of human genetic information as assessed by Southern blotting. In hybrid lines in which human chromosomes were still visible, the most recurrent were numbers 7 and 9. Neither chromosome 7, previously reported to bear some of the genes controlling metastasis in human X mouse T-cell hybrids, nor chromosome 9 appeared to be correlated with the metastatic potential of LF X ICIG hybrids. The same conclusion applied (1) to a human 3.3-kb EcoRI DNA fragment which was amplified (approx. 10-fold) only in metastases induced by one out of 3 metastatic hybrids tested; (2) to the transcription level of c-Ha-ras and c-Ki-ras genes which was enhanced (approx. 4-fold) in metastatic and non-metastatic lines as well. Co-transfection of LF Cl.2A cells with pHSG 272 selectable marker DNA and genomic DNA from normal ICIG-7 human cells or from a hybrid-induced metastasis, reproducibly gave rise to geneticin-resistant transfectants capable of producing spontaneous lung metastases. Neither transfectants nor transfectant-induced metastases harbored detectable human DNA sequences but all harbored pHSG 272 DNA. These results again call for caution in gene transfer studies of the metastatic process.
Cassingena
R
R
UPR 278 CNRS, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Lafarge-Frayssinet
C
C
Frayssinet
C
C
Nardeux
P
P
Estrade
S
S
Viegas-Pequignot
E
E
Dutrillaux
B
B
D000818:Animals; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002459:Cell Fusion / Q000235:genetics; D002875:Chromosomes / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D006822:Hybrid Cells; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics*; D051381:Rats; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D004124:p-Dimethylaminoazobenzene
D004273:DNA, Neoplasm; D004124:p-Dimethylaminoazobenzene