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Tumor burden induces a self-amplifying loop of myelopoiesis that Is mediated by NFκB-kit ligand signaling

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TitleInfo
Title
Tumor burden induces a self-amplifying loop of myelopoiesis that Is mediated by NFκB-kit ligand signaling
Name (type = personal)
NamePart (type = family)
Zhao
NamePart (type = given)
Xin
DisplayForm
XIN ZHAO
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Rabson
NamePart (type = given)
Arnold B
DisplayForm
Arnold B Rabson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Tischfield
NamePart (type = given)
Jay A
DisplayForm
Jay A Tischfield
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
co-chair
Name (type = personal)
NamePart (type = family)
Shao
NamePart (type = given)
Changshun
DisplayForm
Changshun Shao
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Shi
NamePart (type = given)
Yufang
DisplayForm
Yufang Shi
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2012
DateOther (qualifier = exact); (type = degree)
2012-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Cancer cells induce an inflammatory microenvironment which consists of inflammatory cells, cytokines and chemokines. In the meanwhile, malignant tumors are associated with hematological abnormalities that disrupt homeostasis of hematopoiesis. Therefore how tumor burden influence hematopoiesis through inflammatory cytokines is studied in this thesis. Firstly, IFNγ was found to play a major role in lineagelowSca-1+C-kit+ (LSK) cell expansion by activating the expression of Sca-1 in lineagelowSca-1-C-kit+ cells in vivo and in vitro. This process was dependent on IFNγR1 signaling and the STAT1 pathway. The IFNγ-induced LSK cells had a higher proliferation potential than control LSK cells. Moreover, the IFNγ-induced hematopoiesis was more biased toward the differentiation of myeloid lineages. Therefore, our findings demonstrated a novel role of IFNγ in activating hematopoietic progenitor cells and provide a new insight into the clinical application of interferon. Secondly, in tumor-bearing mice, with the decline of hematopoiesis in bone marrow, spleens are greatly enlarged and harbor a greatly expanded population of hematopoietic progenitor cells (HPCs). While such HPCs can differentiate into both myeloid and lymphoid lineages when transplanted into tumor-free hosts, they preferentially give rise to myeloid lineages including macrophages/monocytes in tumor-bearing hosts. We further showed that macrophages/monocytes, derivatives of HPCs, are essential for the expansion of HPCs in spleen. Thus, HPCs and myeloid cells form a positive feedback loop in sustaining splenic myelopoiesis during tumorigenesis. This self-amplifying loop of HPCs and myeloid cells depends on an NFkB-Kit signaling cascade. Tumor-stimulated inflammatory factors are essential for the increased production of Kit ligands by macrophages/monocytes that drives splenic myelopoiesis. Targeting this HPC-myeloid loop may have potential in impeding tumor progression in cancer therapy. In conclusion, we found that the inflammatory cytokine IFNγ was demonstrated to enhance the expansion of hematopoietic stem cells (LSK cells) in vitro and in vivo, which provides important insights into studying the interaction between inflammation and hematopoiesis. Moreover, via mouse tumor models, we revealed the cellular and molecular basis for tumor-induced hematopoiesis and how such abnormal hematopoiesis influenced tumor progression. The information is important to understand the relationship between cancer and hematopoiesis, lending novel hope for cancer therapy.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_3976
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
ix, 120 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Xin Zhao
Subject (authority = ETD-LCSH)
Topic
Cancer cells
Subject (authority = ETD-LCSH)
Topic
Hematopoiesis
Subject (authority = ETD-LCSH)
Topic
Cytokines
Subject (authority = ETD-LCSH)
Topic
Cancer invasiveness
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000065309
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T32N5168
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
ZHAO
GivenName
XIN
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-04-16 00:34:21
AssociatedEntity
Name
XIN ZHAO
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2014-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2014.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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