Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells.
Osteopontin (OPN), bone sialoprotein (BSPII), and osteonectin (ON) belong to a family of glycoproteins, which have been linked to cancer metastasis and progression. Here, we report on the selection of antisense oligonucleotides (ASOs), which are effective in reducing their protein levels. In human MDA-MB-231 breast cancer cells, the maximum inhibition of protein expression ranged from 84% (OPN) to 75% (BSPII) and 70% (ON). Erucylphospho-NNN-trimethylpropanolamine (ErPC3) was used as positive control and combination partner. Exposure to ErPC3 inhibited colony formation of MDA-MB-231 cells by 11% (10 microM), 45% (14 microM) and 78% (20 microM). The clonogenicity of breast cancer cells was reduced by 15%, 11%, 8% (5 microM), 39%, 19%, 14% (10 microM) and 46%, 39%, 21% (20 microM) in response to ASO-OPN-04, ASO-BSPII-06 and ASO-ON-03, respectively. Combination of ErPC3 with the ASOs caused additive combination effects. Pre-exposure to the ASOs, but not to the NSO, inhibited formation of osteolytic metastasis in three of four (ASO-OPN-04, P<0.03) and two of four (ASO-BSPII-06) nude rats, and reduced metastasis lesions significantly (T/C%=4.3 and 9.1, P=0.05, respectively). We conclude that downregulation of OPN and BSPII reduces colony formation of MDA-MB-231 cells and formation of osteolytic metastasis in nude rats.
Adwan
Hassan
H
Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Bäuerle
Tobias J
TJ
Berger
Martin R
MR
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D015676:Osteonectin / Q000378:metabolism; D053495:Osteopontin; D010767:Phosphorylcholine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D012795:Sialoglycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay
C546871:IBSP protein, human; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D016376:Oligonucleotides, Antisense; D015676:Osteonectin; D011412:Propanolamines; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D010767:Phosphorylcholine