In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4892-4892
Abstract:
Introduction: We have previously described motile sperm domain-containing protein 2 (MOSPD2), a protein which up until recently no function was ascribed to, as a key regulator of monocyte migration in-vitro. In this study, the role of MOSPD2 in promoting breast cancer migration and metastasis in-vitro and in-vivo was assessed. Experimental procedure: The prevalence of MOSPD2 was evaluated by IHC in tissue microarray layered with cores, representing different stages of invasiveness in breast cancer. MOSPD2 abundance was scored according to the staining intensity on a scale from 0 to 3. MOSPD2 expression was silenced in MDA-231 breast cancer cell line using lentiviral particles for sh-RNA or CRISPR-CAS9 (CRISPR). Cells were then tested by a trans-well assay for migration towards EGF in vitro as well as for lung dissemination following orthotopic or systemic inoculation in vivo. For mechanism studies, EGF-induced signaling events were analyzed. Results: Within normal adjacent tissue (NAT), 82% of the samples had no staining and the remaining 18% percent displayed an intensity of 1. In the tissue cores with in-situ carcinoma pathology, 79% of the samples had no staining intensity while the remaining 21% only scored 1 or 2. However, analysis of invasive and metastatic cancer demonstrated higher frequency in score of 2 and increased staining intensity up to score of 3 compared with NAT and in-situ carcinoma. Thus, the percent of combined scores 2 and 3 for invasive lobular carcinoma, invasive ductal carcinoma and metastatic invasive ductal carcinoma were 63%, 77% and 81%, respectively. MOSPD2-silenced cells, either by sh-RNA or by CRISPR, were severely impaired in their ability to migrate in-vitro towards EGF. Following EGF activation of CRISPR-Control MDA-231 cells, all tested proteins down-stream to the EGFR pathway, including AKT and p38, became phosphorylated. However, in CRISPR-MOSPD2 silenced cells, phosphorylation of all tested proteins excluding p38 were markedly inhibited. Moreover, activation with IGF of CRISPR-MOSPD2 MDA-231 cells did not hinder AKT phosphorylation. In vivo, SCID mice injected orthotopically or systemically with CRISPR-MOSPD2 silenced MDA-231 cells displayed significantly reduced number of metastases in the lungs relatively to mice injected with CRISPR-Control treated cells. Conclusions: We suggest that MOSPD2 promotes metastasis of breast cancer cells and is a potential target for the treatment of metastatic breast cancer. Citation Format: Itzhak Mendel, Yaniv Salem, Niva Yacov, Oshrat Propheta-Meiran, Eyal Breitbart. MOSPD2, a newly characterized protein, promotes breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4892. doi:10.1158/1538-7445.AM2017-4892
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-4892
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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