Targeting cancer cell adhesion molecule, CD146, with low-dose gold nanorods and mild hyperthermia disrupts actin cytoskeleton and cancer cell migration

Abstract

Cluster of differentiation 146 (CD146), a cancer cell adhesion molecule, is over-expressed on the surfaces of melanoma, breast, ovarian, and prostate cancer cells, and its high expression indicates the migration tendency of these cancer cells and poor patient prognosis. Here, we hypothesize that targeting the CD146 with low-dose gold nanorods combined with mild hyperthermia can stop the migration of these cancer cells. Two metastatic cancer cells including a melanoma and a breast cancer cell line are selected as the model systems. Cell migration assays show that the migration of both cell lines can be completely stopped by the treatment. Atomic force microscopy and super resolution fluorescence microscopy reveal the alterations of actin cytoskeleton and cell morphology correspond to the inhibited cell migration. Further mechanistic analysis indicates the treatment disrupts the actin cytoskeleton by a synergistic mechanism including depleting membrane CD146 and interfering ezrin-radixin-moesin phosphorylation. As a result, we believe targeting CD146 with low-dose gold nanorods and mild hyperthermia could be a versatile, effective, and safe approach for stopping cancer metastasis. More broadly, the concept of targeting cancer cell surface markers that connect the underlying actin cytoskeleton, offers enormous potential in treating cancer metastasis, which accounts for more than 90% of cancer-associated mortality.