To investigate whether maspin, when produced at endogenous levels, is capable of inhibiting metastasis to bone we transfected a bacterial artificial chromosome (BAC) genomic clone containing the maspin gene into PC-3 cells that aggressively metastasize to bone in an animal model.
Transfection of MDA-MB-435 mammary carcinoma cells with the maspin gene did not alter the cells' growth properties in vitro, but reduced the cells' ability to induce tumors and metastasize in nude mice and to invade through a basement membrane matrix in vitro.
Finally, engineered alterations in the expression of two of the epithelial genes (SERPINB5 and LTF) modified cell motility in vitro, in accordance with a possible causal role in metastasis.
Of the investigated metastasis suppressor genes, only higher AKAP12 mRNA expression was correlated with decreased metastasis (P < 0.05) and invasion scores (P < 0.01) while higher SERPINB5 mRNA expression was correlated with increased metastasis scores (P < 0.05).
Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS1, a metastasis suppressor gene, in the treated group.