Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel.
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.
Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, United States.
Gladys N
GN
Nangami
Kurt
K
Watson
Kitani
K
Parker-Johnson
Kelechi O
KO
Okereke
Amos
A
Sakwe
Pamela
P
Thompson
Nanna
N
Frimpong
Josiah
J
Ochieng
D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D010958:Plasminogen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
D001672:Biocompatible Materials; D054377:Chemokine CXCL12; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D060749:alpha-2-HS-Glycoprotein; C059485:matrigel; D010958:Plasminogen; D003094:Collagen
Chemo-attraction; Chemo-invasion; Chemotaxis; Exosomes; Fetuin-A; Gradient