東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back to Search results for [ null ]

Switch To: Labeled | MARC Mode | ISBD

Linked to FindBook

Google Book

Amazon

博客來

Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer./
Author:	Tsai, Kun-Chih Kelvin.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2005,
Description:	142 p.
Notes:	Source: Dissertations Abstracts International, Volume: 67-11, Section: B.
Contained By:	Dissertations Abstracts International67-11B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3194470
ISBN:	9780542392719

Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer.
Tsai, Kun-Chih Kelvin.

Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2005 - 142 p.

Source: Dissertations Abstracts International, Volume: 67-11, Section: B.

Thesis (Ph.D.)--Harvard University, 2005.

This item is not available from ProQuest Dissertations & Theses.

Ample evidence suggests that the stromal microenvironment in which tumor cells develop profoundly influences many steps of epithelial tumorigenesis. Fibroblasts, a major cell type of the stromal compartment, may function as a stress monitor to interact with epithelial cells and to modulate their response. The molecular details of the epithelium-stroma interaction, however, remain not well understood. We here demonstrate that fibroblasts engage in a senescence-like cellular program in response to cumulative sublethal stress insults. We further show that the accumulation of senescence-like fibroblasts in the stroma can compromise the mammary tissue homeostasis and deregulate epithelial-stromal interactions. Using protracted low-dose ionizing radiation (IR) as a model of low-level environmental stress, we demonstrate that primary human mammary stromal fibroblasts (HMFs) respond to low-dose IR by displaying a senescence-like phenotype in a dose-dependent and accumulative manner. Compared with un-irradiated HMFs, IR-induced senescence-like fibroblasts (SFs) profoundly stimulate the growth of malignant mammary epithelial cells (MECs) in a two-dimensional coculture assay. In agreement with the growth promoting activity, functional genomic analysis reveals that SFs transmit mitogenic signals to MECs by upregulating mitotic regulators. To further understand the heterotypic influences of SFs on MECs, we adopted a three-dimensional (3D) coculture system to study the epithelial-stromal interactions in a tissue-like context. We provide a direct experimental proof that SFs dysregulate the 3D growth of MECs due to the substantial cytoskeletal alterations in SFs and the upregulation of multiple secreted-type matrix metalloproteinases. The resultant alterations in cell-cell and cell-matrix interactions lead to aberrant proliferation, tissue morphogenesis, matrix invasion and stress responses of MECs depending on their genetic status. Untransformed MECs respond to SFs by growing into enlarged cysts with central cell-free lumens; MECs with inactivated apoptosis- and autophagy-dependent cell death pathways formed filled masses that resemble incipient tumors; malignant MECs that have undergone epithelial-mesenchymal transition fully express their invasive potential in the presence of SFs. Taken together, our results suggest that low-level environmental stress can foster an oncogenic environment that interacts with permissive genetic traits in epithelial cells to promote breast carcinogenesis.

ISBN: 9780542392719Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Aging

Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer.
LDR:04016nmm a2200445 4500 001 2342278
005 20220311105627.5
008 241004s2005 ||||||||||||||||| ||eng d
020 $a 9780542392719
035 $a (MiAaPQ)AAI3194470
035 $a AAI3194470
040 $a MiAaPQ $c MiAaPQ
100 1 $a Tsai, Kun-Chih Kelvin. $3 3680616
245 1 0 $a Heterotypic cell interactions between stress-induced prematurely senescent mammary stroma and neighboring epithelial cells in aging and breast cancer.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2005
300 $a 142 p.
500 $a Source: Dissertations Abstracts International, Volume: 67-11, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Yuan, Zhi-Min.
502 $a Thesis (Ph.D.)--Harvard University, 2005.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Ample evidence suggests that the stromal microenvironment in which tumor cells develop profoundly influences many steps of epithelial tumorigenesis. Fibroblasts, a major cell type of the stromal compartment, may function as a stress monitor to interact with epithelial cells and to modulate their response. The molecular details of the epithelium-stroma interaction, however, remain not well understood. We here demonstrate that fibroblasts engage in a senescence-like cellular program in response to cumulative sublethal stress insults. We further show that the accumulation of senescence-like fibroblasts in the stroma can compromise the mammary tissue homeostasis and deregulate epithelial-stromal interactions. Using protracted low-dose ionizing radiation (IR) as a model of low-level environmental stress, we demonstrate that primary human mammary stromal fibroblasts (HMFs) respond to low-dose IR by displaying a senescence-like phenotype in a dose-dependent and accumulative manner. Compared with un-irradiated HMFs, IR-induced senescence-like fibroblasts (SFs) profoundly stimulate the growth of malignant mammary epithelial cells (MECs) in a two-dimensional coculture assay. In agreement with the growth promoting activity, functional genomic analysis reveals that SFs transmit mitogenic signals to MECs by upregulating mitotic regulators. To further understand the heterotypic influences of SFs on MECs, we adopted a three-dimensional (3D) coculture system to study the epithelial-stromal interactions in a tissue-like context. We provide a direct experimental proof that SFs dysregulate the 3D growth of MECs due to the substantial cytoskeletal alterations in SFs and the upregulation of multiple secreted-type matrix metalloproteinases. The resultant alterations in cell-cell and cell-matrix interactions lead to aberrant proliferation, tissue morphogenesis, matrix invasion and stress responses of MECs depending on their genetic status. Untransformed MECs respond to SFs by growing into enlarged cysts with central cell-free lumens; MECs with inactivated apoptosis- and autophagy-dependent cell death pathways formed filled masses that resemble incipient tumors; malignant MECs that have undergone epithelial-mesenchymal transition fully express their invasive potential in the presence of SFs. Taken together, our results suggest that low-level environmental stress can foster an oncogenic environment that interacts with permissive genetic traits in epithelial cells to promote breast carcinogenesis.
590 $a School code: 0084.
650 4 $a Cellular biology. $3 3172791
650 4 $a Molecular biology. $3 517296
650 4 $a Oncology. $3 751006
653 $a Aging
653 $a Breast cancer
653 $a Epithelial cells
653 $a Heterotypic
653 $a Mammary
653 $a Senescent
653 $a Stress-induced
653 $a Stroma
690 $a 0379
690 $a 0307
690 $a 0992
710 2 $a Harvard University. $3 528741
773 0 $t Dissertations Abstracts International $g 67-11B.
790 $a 0084
791 $a Ph.D.
792 $a 2005
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3194470