title: Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice.
abstract: Semaphorins are a large family of molecules involved in axonal guidance during the development of the nervous system and have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A) has been reported to have a chemotactic activity in neurogenesis and to be an immune modulator through α1β1integrins. SEMA7A has been shown to promote monocyte chemotaxis and induce them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in a murine model of breast cancer. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4), and that peritoneal elicited macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to those derived from normal mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecule CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2/MIP-2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p < 0.01) lower levels of angiogenic proteins, such as CXCL2/MIP-2, CXCL1, and MMP-9, compared to those from control DA-3 mammary tumors. We postulate that SEMA7A in mammary carcinomas may skew monocytes into a pro-tumorigenic phenotype to support tumor growth. SEMA7A could prove to be valuable in establishing new research avenues toward unraveling important tumor-host immune interactions in breast cancer patients.
authors.affiliation: Tumor Immunology, Department of Biomedical Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Garcia-Areas
authors.affiliation: Tumor Immunology, Department of Biomedical Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Stephania
authors.initials: S
authors.lastname: Libreros
authors.affiliation: Tumor Immunology, Department of Biomedical Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Amat
authors.affiliation: Immunology, Department of Biological Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keating
authors.affiliation: Tumor Immunology, Microbiology and Immunology, University of Miami Miller School of Medicine Miami, FL, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrio
authors.affiliation: Department of Clinical Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Robinson
authors.affiliation: Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami Miller School of Medicine Miami, FL, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Blieden
authors.affiliation: Tumor Immunology, Department of Biomedical Sciences, Florida Atlantic University Boca Raton, FL, USA.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Iragavarapu-Charyulu
keywords: CXCL2/MIP-2; MMP-9; SEMA7A; angiogenesis; breast cancer; macrophages