Solid tumors can hijack many of the same programs used in neurogenesis
to enhance tumor growth and metastasis, thereby generating a plethora of
neurogenesis-related molecules including semaphorins Among them, we have
identified Semaphorin7A (SEMA7A) in breast cancer We first used to the DA-3
mammary tumor model to determine the effect of tumor-derived SEMA7A on
immune cells We found that tumor-derived SEMA7A can modulate the
production of proangiogenic chemokines CXCL2/MIP-2 and CXCL 1, and prometastatic
MMP-9 in macrophages We next aimed to determine the expression
and function of SEMA7A in mammary tumor cells We found that SEMA7A is
highly expressed in both metastatic human and murine breast cancer cells We
show that both TGF-β and hypoxia elicits the production of SEMA 7 A in mammary
cells SEMA7 A shRNA silencing in 4T1 cells resulted in decreased mesenchymal
markers MMP-3, MMP-13, Vimentin and TGF-β) SEMA7A silenced cells show increased stiffness with reduced migratory and proliferative potential In vivo,
SEMA7A silenced 4T1 tumor bearing mice showed decreased tumor growth and
metastasis Genetic ablation of host-derived SEMA7A synergized to further
decrease the growth and metastasis of 4T1 cells Our findings suggest novel
functional roles for SEMA7A in breast cancer and that SEMA7A could be a novel
therapeutic target to limit tumor growth and metastasis / Includes bibliography / Dissertation (PhD)--Florida Atlantic University, 2016 / FAU Electronic Theses and Dissertations Collection
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_33916 |
| Contributors | Garcia-Areas, Ramon A. (author), lragavarapu-Charyulu, Vijaya (Thesis advisor), Florida Atlantic University (Degree grantor), Charles E Schmidt College of Science, Department of Biomedical Science |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 96 p, application/pdf |
| Rights | Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder, http://rightsstatements.org/vocab/InC/1.0/ |
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