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A novel immunosuppressive pathway mediated by chitinase-3-like-1 protein in a model of breast cancer
Title
A novel immunosuppressive pathway mediated by chitinase-3-like-1 protein in a model of breast cancer.
Creator
Libreros, Stephania, Garcia-Areas, Ramon A., Iragavarapu-Charyulu, Vijaya, Graduate College
Date Issued
2011-04-08
PURL
http://purl.flvc.org/fcla/dt/3164613
Subject Headings
Immunosuppression, Chitinase, Breast --Cancer
Format
Document (PDF)
Hypoxia Inducible Factor-Alpha Promotes Expression of Pro-tumorigenic Semaphorin7A in Mammary Tumor Cells
Title
Hypoxia Inducible Factor-Alpha Promotes Expression of Pro-tumorigenic Semaphorin7A in Mammary Tumor Cells.
Creator
Karram, Joseph P., Garcia-Areas, Ramon A., Libreros, Stephania, Graduate College, Castro, C., Keating, Patricia, Iragavarapu-Charyulu, Vijaya
Abstract/Description
It is estimated that one in eight women will be diagnosed with breast cancer. Developing an understanding of the tumor microenvironment is critical for developing treatments for breast cancer patients. It has been well established that hypoxia, or a lack of oxygen, is fundamental in creating a microenvironment that enables metastasis via eliciting angiogenic processes. Poorly differentiated blood vessels can fashion an oxygen-deprived microenvironment that triggers the expression of...
Show moreIt is estimated that one in eight women will be diagnosed with breast cancer. Developing an understanding of the tumor microenvironment is critical for developing treatments for breast cancer patients. It has been well established that hypoxia, or a lack of oxygen, is fundamental in creating a microenvironment that enables metastasis via eliciting angiogenic processes. Poorly differentiated blood vessels can fashion an oxygen-deprived microenvironment that triggers the expression of transcription factor Hypoxia Inducible Factor alpha HIF-1alpha that in turn can up regulate genes mediating a protumor effect. Our laboratory has discovered that mammary tumors express Semaphorin7a SEMA7A, a HIF-1alpha inducible protein. This study’s objective is to delineate the mechanism for hypoxia induction in mammary cells. Cobalt Chloride CoCl2 was used to mimic hypoxia in mammary tumor cell cultures. Flow cytometry was used to determine HIF-1alpha activity in the mammary cells. Benign EpH4 mammary cells expressing low SEMA7A greatly increased its expression after response to hypoxic stimuli as determined by qPCR and SEMA7A-specific ELISA. Pretreatment of EpH4 cells with a HIF-1alpha inhibitor Chemotin blocked induction of SEMA7A. Paradoxically, CoCl2 did not raise expression in the highly metastatic 4T1 cells which experience high levels of SEMA7A. Treatment of 4T1 cells with Chemotin under normoxic conditions inhibit HIF-1alpha activity and decrease SEMA7A levels. Determining the role of SEMA7A in the hypoxia axis could further elucidate novel pathways in breast cancer, suggesting that malignant tumor cells can utilize HIF-1alpha in a hypoxic independent manner.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00005887
Format
Document (PDF)
Exploring the role of CHI3L1 in “pre-metastatic” lungs of mammary tumor-bearing mice
Title
Exploring the role of CHI3L1 in “pre-metastatic” lungs of mammary tumor-bearing mice.
Creator
Libreros, Stephania, Garcia-Areas, Ramon A., Keating, Patricia, Carrio, Roberto, Iragavarapu-Charyulu, Vijaya
Date Issued
2013
PURL
http://purl.flvc.org/fau/fd/FAUIR000157
Format
Citation
Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice
Title
Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice.
Creator
Garcia-Areas, Ramon A., Libreros, Stephania, Amat, Samantha, Keating, Patricia, Carrio, Roberto, Robinson, Phillip, Blieden, Clifford, Iragavarapu-Charyulu, Vijaya
Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FAUIR000158
Format
Citation
Elucidating the role of Semaphorin 7A in breast cancer
Title
Elucidating the role of Semaphorin 7A in breast cancer.
Creator
Garcia-Areas, Ramon A., lragavarapu-Charyulu, Vijaya, Florida Atlantic University, Charles E Schmidt College of Science, Department of Biomedical Science
Abstract/Description
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...
Show moreSolid 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
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004802
Subject Headings
Breast--Cancer--Diagnosis, Semaphorins, Protein precursors, Cellular signal transduction, Cell receptors
Format
Document (PDF)