ALCAM, activated leukocyte cell adhesion molecule, influences the aggressive nature of breast cancer cells, a potential connection to bone metastasis

Abstract

Introduction: ALCAM, activated leukocyte cell adhesion molecule, is connected to the progression of certain solid tumours and has been shown to be a prominent feature for tumours that subsequently developed bone metastasis. The present study investigated the biological influence of ALCAM on breast cancer cells in connection with bone biological environment.

Materials and methods: Suitable breast cancer cells were transfected with either the ALCAM expression construct or anti-ALCAM transgene, to create sublines that had differential expression of ALCAM. The growth, migration and invasion of the cells were evaluated in the presence or absence of matrix proteins prepared from human bones.

Results: ZR-751(DeltaALCAM) (ALCAM knockdown) and MDA-MB-231(ALCAMexp) (overexpressing ALCAM) were constructed. MDA MB-231(ALCAMexp) cells showed a slower rate of growth compared with control cells. However, in the presence of bone matrix proteins, MDA MB-231(ALCAMexp) showed a significantly reduced rate of growth, p<0.01 vs. control cells. In contrast, ZR-751(DeltaALCAM) cells grew faster compared with control cells. MDA MB-231(ALCAMexp) displayed a significantly reduced (p=0.012) and ZR-751(DeltaALCAM) cells significantly increased invasiveness (p=0.02) vs. their respective controls cells. In an ECIS-based cell migration assay, MDA-MB-231(ALCAMexp) cells showed marked reduction in migration. Inclusion of bone matrix proteins therefore further reduced the migration speed of MDA MB-231(ALCAMexp) cells.

Conclusion: Loss of ALCAM in breast cancer cells facilitates the invasive behaviour of breast cancer and high levels of ALCAM in the cells have a suppressive role in the aggressive nature of breast cancer cells.