Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells

KAI1 is a metastasis suppressor gene for human prostate cancer and is also involved in the progression of a variety of other human cancers. Previously ,, we have demonstrated that KAI1 expression was down-regulated in metastat ic breast cancer cell lines as well as in highly aggressive breast cancer s pecimens, To determine whether KAI1 expression is responsible for the metas tasis suppression in breast cancer, me transfected the human KAI1 cDNA into two highly malignant breast cancer cell lines, LCC6 and MDA-MB-231, which both have low levels of endogenous KAI1 expression. Parental, vector-only t ransfectants and KAII transfectant clones were injected into the mammary fa t pads and tail veins, respectively, of athymic nude mice and assessed for both spontaneous and experimental lung metastasis, High KBI1 expression sig nificantly suppressed the metastatic potential of KAI1-transfected LCC6 cel ls. Metastasis suppression correlated with the reduced rate of tumor growth and a decreased clonogenicity in soft agar, Furthermore, KAI1 expression s ignificantly suppressed the in vitro cell invasion in KAI1-transfected MDA- MB-231 cells. Our results suggested that KAI1 may function as a negative re gulator of breast cancer metastasis.