Decreased levels of osteopontin and bone sialoprotein II are correlated with reduced proliferation, colony formation, and migration of GFP-MDA-MB-231 cells.
MDA-MB-231 human breast cancer cells transfected with GFP were used as model to determine the reduction in proliferation, colony formation, and migration in response to agents with anti-metastatic properties. These agents consisted of antisense oligonucleotides (ASOs) directed against osteopontin (OPN), bone sialoprotein II (BSP II), and osteonectin (ON), as well as an antibody directed against BSP II. A bisphosphonate derivative (ibandronate) and an alkylphosphocholine (erucylphospho-NNN-trimethylpropanolamine; ErPC3) were used as positive controls. The ASOs directed against OPN, BSP II and ON suppressed the expression of their respective target proteins by 81%, 74% and 69%, respectively. They were barely but significantly active in inhibiting the proliferation, but intermediately to highly active in inhibiting the colony formation and migration of GFP-MDA-MB-231 breast cancer cells. The antibody against human BSP II was significantly more active than all ASOs used and was equally active or even surpassed the activity of ibandronate and ErPC3 in all three assays. The results obtained suggest a specific anti-metastatic activity of this antibody as well as of the ASOs found effective in decreasing OPN and BSP II expression.
Adwan
Hassan
H
Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, D-69120 Heidelberg, Germany.
Bäuerle
Tobias
T
Najajreh
Yousef
Y
Elazer
Victoria
V
Golomb
Gershon
G
Berger
Martin R
MR
D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002648:Child; D003114:Colony-Forming Units Assay; D004164:Diphosphonates / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D000077557:Ibandronic Acid; D007074:Immunoglobulin G / Q000494:pharmacology; D058574:Integrin-Binding Sialoprotein; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010755:Organophosphates / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000378:metabolism*
D004164:Diphosphonates; C546871:IBSP protein, human; D007074:Immunoglobulin G; D058574:Integrin-Binding Sialoprotein; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D053495:Osteopontin; D049452:Green Fluorescent Proteins; D000077557:Ibandronic Acid