期刊
ONCOTARGET
卷 6, 期 33, 页码 34071-34086出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6049
关键词
Nodal; cancer; antibody; ELISA; therapy
资金
- NIH [RO1CA121205, R37CA59702]
- H Foundation
- Dixon Translational Research Grant
- Brinson Foundation
- FIRB MERIT [RBNE08NKH7_003]
- PON Ricerca e Competitivita [PON01_01602, PON01_02342]
- ACS-IRG [93-037-18]
Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.
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