Suppression of tumor-derived Semaphorin 7A and genetic ablation of host-derived Semaphorin 7A impairs tumor progression in a murine model of advanced breast carcinoma

Garcia-Areas,R.; Libreros,S.; Simoes,M.; Castro-Silva,C.; Gazaniga,N.; Amat,S.; Jaczewska,J.; Keating,P.; Schilling,K.; Brito,M.; Wojcikiewicz,E. P.; Iragavarpu-Charyulu,V.

doi:10.3892/ijo.2017.4144

Suppression of tumor-derived Semaphorin 7A and genetic ablation of host-derived Semaphorin 7A impairs tumor progression in a murine model of advanced breast carcinoma

Authors:
- R. Garcia-Areas
- S. Libreros
- M. Simoes
- C. Castro-Silva
- N. Gazaniga
- S. Amat
- J. Jaczewska
- P. Keating
- K. Schilling
- M. Brito
- E. P. Wojcikiewicz
- V. Iragavarpu-Charyulu
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Affiliations: Department of Biomedical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA, Lynn Women's Health & Wellness Institute, Boca Raton Regional Hospital, Boca Raton, FL 33431, USA, Department of Pathology, Boca Raton Regional Hospital, Boca Raton, FL 33431, USA
Published online on: October 3, 2017 https://doi.org/10.3892/ijo.2017.4144
Pages: 1395-1404
Copyright: © Garcia-Areas et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Solid tumors can generate a plethora of neurogenesis-related molecules that enhance their growth and metastasis. Among them, we have identified axonal guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1 murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors exhibited decreased growth rates, deferred metastasis and reduced mortality. In vitro, SEMA7A shRNA-expressing 4T1 cells had weakened proliferative, migratory and invasive abilities, and decreased levels of mesenchymal factors. Atomic force microscopy studies showed that SEMA7A shRNA-expressing 4T1 cells had an increase in cell stiffness that corresponded with their decreased malignant potential. Genetic ablation of host-derived SEMA7A further enhanced the antitumor effects of SEMA7A shRNA gene silencing in 4T1 cells. Our preclinical findings demonstrate a critical role for SEMA7A in mediating mammary tumor progression.

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