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Cell Rep. 2014 Oct 9;9(1):118-128. doi: 10.1016/j.celrep.2014.08.042. Epub 2014 Sep 25.

SDF-1 inhibition targets the bone marrow niche for cancer therapy.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
2
NOXXON Pharma AG, 10589 Berlin, Germany.
3
Department of Pathology, University of Brescia Medical School, Spedali Civili di Brescia, 25123 Brescia, Italy.
4
Spedali Civili di Brescia, Department of Hematology, Centro per la Ricerca Onco-ematologica AIL, (CREA), 25123 Brescia, Italy.
5
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: irene_ghobrial@dfci.harvard.edu.

Abstract

Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active MM, as well as in BM sites of tumor metastasis and report on the discovery of the high-affinity anti-SDF-1 PEGylated mirror-image l-oligonucleotide (olaptesed-pegol). In vivo confocal imaging showed that SDF-1 levels are increased within MM cell-colonized BM areas. Using in vivo murine and xenograft mouse models, we document that in vivo SDF-1 neutralization within BM niches leads to a microenvironment that is less receptive for MM cells and reduces MM cell homing and growth, thereby inhibiting MM disease progression. Targeting of SDF-1 represents a valid strategy for preventing or disrupting colonization of the BM by MM cells.

PMID:
25263552
PMCID:
PMC4194173
DOI:
10.1016/j.celrep.2014.08.042
[Indexed for MEDLINE]
Free PMC Article

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