SUPPRESSION OF MDA-MB-435 BREAST-CARCINOMA CELL METASTASIS FOLLOWING THE INTRODUCTION OF HUMAN-CHROMOSOME-11

To determine the relevance of genetic information on chromosome 11 in the development of metastatic breast tumors, we introduced a normal hu man chromosome 11 into the highly metastatic MDA-MB-435 breast carcino ma cell line via the microcell-mediated chromosome transfer technique. Although the MDA-MB-435 recipient cell line and four randomly selecte d microcell hybrid clones remained tumorigenic in nude mice, the hybri ds were >95% suppressed for metastasis to lung and regional lymph node s (P < 0.01). We also tested whether chromosome 6 harbors a metastasis -suppressor gene for breast cancer as observed previously for human me lanoma. Grouped together, the four neo6 microcell hybrids had no stati stically significant reduction in the incidence or number of lung or l ymph node metastases compared to the weakly metastatic, subcloned pare nt cell line, MDA-MB-435.7. Expression of nm23-H1 (NME1), a known meta stasis-suppressor gene in this breast cancer cell line, did not correl ate with metastasis suppression in the microcell hybrids. These result s further demonstrate that control of metastasis is molecularly distin ct from tumorigenic potential. They also indicate that chromosome 11 e ncodes a metastasis-suppressor gene for human breast cancer.