Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel

• DOI: 10.1016/j.bbrc.2013.07.125
• Publication Date: 2013-08-07T16:45:42Z
• Authors: Gladys N. Nangami; Kurt Watson; KiTani Parker-Joh...; Kelechi O. Okereke; Amos Sakwe; Pamela Thompson; Nanna Frimpong; Josiah Ochieng
• Keywords: 0303 health sciences; Colon; alpha-2-HS-Glycoprotein; Chemotaxis; Biocompatible Materials; Breast Neoplasms; Plasminogen; Chemokine CXCL12; Drug Combinations; 03 medical and health sciences; Cell Line, Tumor; Colonic Neoplasms; Animals; Humans; Cattle; Female; Neoplasm Invasiveness; Proteoglycans; Breast; Collagen; Laminin

The present study was conducted to determine whether fetuin-A, a dominant serum protein plays a role in chemo-attraction and chemo-invasion of carcinoma cells in vitro. Serum is normally used as positive chemotaxis control in Boyden chamber motility assays, prompting the need to identify the factor/s in serum that contributes the bulk of chemo-taxis and invasion. Serum has a plethora of chemotactic factors including stromal derived factor 1 also known as CXCL12. Using highly purified fetuin-A, we compared its chemo-attraction potential to culture medium containing 10% fetal bovine serum. We also investigated its ability to attract tumor cells through a bed of Matrigel (invasion assay). We demonstrated, using similar concentration range of fetuin-A found in blood, that it robustly supports both directed chemo-attraction and invasion of breast tumor cells. More importantly, we showed that at low concentrations (fetuin-A coated wells) itinteracts synergistically with CXCL12 to promote chemotaxis. The presence of plasminogen (PL) blunted the fetuin-A mediated chemotaxis. Taken together, the data suggest an in vivo chemotaxis/invasion role for fetuin-A.