Mechanisms of metastasis suppression by introduction of human chromosome 10 into rat prostate cancer.
OBJECTIVE
The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones).


METHODS
Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed.


RESULTS
Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone.


CONCLUSIONS
The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.
Hamano
Masaaki
M
Department of Molecular Oncology (M7), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Kuramochi
Hiroaki
H
Nihei
Naoki
N
Kamiya
Naoto
N
Suzuki
Hiroyoshi
H
Igarashi
Tatsuo
T
Barrett
J Carl
JC
Ichikawa
Tomohiko
T
Ito
Haruo
H
D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division; D002879:Chromosomes, Human, Pair 10; D005780:Gelatin / Q000032:analysis; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051381:Rats; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D014407:Tumor Cells, Cultured
D005780:Gelatin