CHROMOSOME 17-MEDIATED DORMANCY OF AT6.1 PROSTATE-CANCER MICROMETASTASES

To improve the diagnosis and treatment of cancer, an increased underst anding of the molecular and cellular changes that regulate metastatic ability is required. We have recently demonstrated a prostate cancer m etastasis-suppressor activity encoded by a discontinuous similar to 70 -cM region of human chromosome. The presence of this region suppresses the spontaneous metastatic ability of AT6.1 rat prostatic cancer cell s by greater than 30-fold (M. A. Chekmareva et at, Prostate, 33: 271-2 80, 1997), Interestingly, a number of potentially important genes whic h have been mapped to human chromosome 17, including TP53, NM23, and B RCA1, are not retained (M. A. Chekmareva st al., cited above) or are n ot expressed in these microcell hybrids (B. A. Yoshida st at, In Vivo; in press), which suggests the presence of a novel metastasis-suppress or gene(s) or novel function of a known gene(s) encoded by this region (s). We hypothesize that identification of the ''step'' in the metasta tic cascade that is inhibited by the presence of the similar to 70-cM metastasis-suppressor region will facilitate the identification of can didate metastasis-suppressor genes. For a cancer cell to metastasize, it must escape from the primary tumor, enter the circulation, arrest i n the microcirculation, extravasate into a tissue compartment, and gro w. This suppression of spontaneous macroscopic lung metastases could b e due to the inhibition of a number of steps within this cascade. Resu lts of the current study demonstrate that AT6.1 cells containing the s imilar to 70-cM region (AT6.1-17-4 cells) escape from the primary tumo r and arrest in the lung but are growth-inhibited unless the metastasi s-suppressor region is Lost. This growth inhibition seems to result fr om an effect of one or more genes at the metastatic site and not from a circulating angiogenesis inhibitor. Our findings suggest that the si milar to 70-cM region of human chromosome 17 may encode a gene(s) that regulates the ''dormancy'' of AT6.1-17-4 micrometastases.