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Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells

Cancer Gene Therapy volume 11, pages 109–120 (2004)Cite this article

Abstract

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 μM), 45% (14 μM) and 78% (20 μM). The clonogenicity of breast cancer cells was reduced by 15%, 11%, 8% (5 μM), 39%, 19%, 14% (10 μM) and 46%, 39%, 21% (20 μM) 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.

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Abbreviations

OPN:

osteopontin

BSPII:

bone sialoprotein II

ON:

osteonectin

ErPC3:

Erucylphospho-NNN-trimethylpropanolamine

ASO:

antisense oligonucleotide

NSO:

nonsense oligonucleotide

SIBLING:

small integrin-binding ligand∧N-linked glycoprotein

ECM:

extracellular matrix

FBS:

fetal bovine serum

HUSAR:

Heidelberg UNIX sequence Analysis Resource

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Acknowledgements

The experiments described were performed within the framework of the DKFZ Heidelberg-MOS Israel cooperation in cancer research and one of the authors (HA) was funded by a grant from this cooperation.

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  1. Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Hassan Adwan, Tobias J Bäuerle & Martin R Berger

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  1. Hassan Adwan
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Correspondence to Martin R Berger.

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Adwan, H., Bäuerle, T. & Berger, M. Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene Ther 11, 109–120 (2004). https://doi.org/10.1038/sj.cgt.7700659

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