To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer
博士 === 國防醫學院 === 醫學科學研究所 === 105 === CD164, a sialomucin, also known as endolyn or MGC-24 (24 kDa multi-glycosylated core protein), was a cell adhesion molecule which regulates proliferation, adhesion, and differentiation of hematopoietic stem cells. Emerging evidences indicated that the expression...
Main Authors: | , |
---|---|
Other Authors: | |
Format: | Others |
Language: | en_US |
Published: |
2016
|
Online Access: | http://ndltd.ncl.edu.tw/handle/sva958 |
id |
ndltd-TW-105NDMC0659006 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TW-105NDMC06590062019-05-15T23:09:05Z http://ndltd.ncl.edu.tw/handle/sva958 To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer 探討CD164於肺癌 腫瘤生成與幹細胞特性之角色 CHEN, WEI-LIANG 陳韋良 博士 國防醫學院 醫學科學研究所 105 CD164, a sialomucin, also known as endolyn or MGC-24 (24 kDa multi-glycosylated core protein), was a cell adhesion molecule which regulates proliferation, adhesion, and differentiation of hematopoietic stem cells. Emerging evidences indicated that the expression of CD164 was involved in the tumorigenesis and cancer progression in colon, prostate and ovarian cancers. However, few data were available regarding the clinical significance of CD164 expression in lung cancer. The objective of this study was to investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer. The expression of CD164 in the normal human bronchial epithelium (BEAS-2B cell) and several lung cancer cell lines were examined by immunoblotting analysis firstly. Using the tissue microarrays, CD164 expression is correlated with clinicopathological characteristics in human lung cancer. To elucidate the transforming effect of CD164 on the morphology, proliferation, stemness in normal lung cells, we overexpressed the CD164 in cell lines infected by lentivirus-expressing pWPXL-vector with human CD164 coding sequence. Overexpression of CD164 in normal lung epithelial cell (BEAS2B cell) not only leads to malignant transformation in vitro and tumorigenicity in the xenografted mice but also induces the stem cell-like property and drug resistance. CD164 expression was involved in the drug resistance through modulation of ATP-binding cassette transporters, including ABCG2 (BCRP) and ABCB1 (p-glycoprotein/MDR1). Overexpression of CD164 activates AKT/mTOR signaling to increased CXCR4 expression. Because the PI3K/Akt/mTOR pathway was a prototypic survival pathway in many types of cancer, we administrated mTOR inhibitor (Rapamycin) in vitro and in vivo studies to clarify the significance of mTOR pathway in the tumorigenesis and stemness of the lung cancer. Rapamycin, mTOR inhibitor, hinders the cell proliferation along with sphere formation in vitro and impedes the tumor growth in vivo. In conclusion, we provide several lines of evidence that the CD164 promotes lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance mediated through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell marker would possibly provide valuable approaches to develop effective therapy for lung cancer, especially for chemoresistant cancers which highly express CD164 using rapamycin as adjuvant therapy. James Yi-Hsin Chan 詹益欣教授 2016 學位論文 ; thesis 21 en_US |
collection |
NDLTD |
language |
en_US |
format |
Others
|
sources |
NDLTD |
description |
博士 === 國防醫學院 === 醫學科學研究所 === 105 === CD164, a sialomucin, also known as endolyn or MGC-24 (24 kDa multi-glycosylated core protein), was a cell adhesion molecule which regulates proliferation, adhesion, and differentiation of hematopoietic stem cells. Emerging evidences indicated that the expression of CD164 was involved in the tumorigenesis and cancer progression in colon, prostate and ovarian cancers. However, few data were available regarding the clinical significance of CD164 expression in lung cancer. The objective of this study was to investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer.
The expression of CD164 in the normal human bronchial epithelium (BEAS-2B cell) and several lung cancer cell lines were examined by immunoblotting analysis firstly. Using the tissue microarrays, CD164 expression is correlated with clinicopathological characteristics in human lung cancer. To elucidate the transforming effect of CD164 on the morphology, proliferation, stemness in normal lung cells, we overexpressed the CD164 in cell lines infected by lentivirus-expressing pWPXL-vector with human CD164 coding sequence. Overexpression of CD164 in normal lung epithelial cell (BEAS2B cell) not only leads to malignant transformation in vitro and tumorigenicity in the xenografted mice but also induces the stem cell-like property and drug resistance. CD164 expression was involved in the drug resistance through modulation of ATP-binding cassette transporters, including ABCG2 (BCRP) and ABCB1 (p-glycoprotein/MDR1). Overexpression of CD164 activates AKT/mTOR signaling to increased CXCR4 expression. Because the PI3K/Akt/mTOR pathway was a prototypic survival pathway in many types of cancer, we administrated mTOR inhibitor (Rapamycin) in vitro and in vivo studies to clarify the significance of mTOR pathway in the tumorigenesis and stemness of the lung cancer. Rapamycin, mTOR inhibitor, hinders the cell proliferation along with sphere formation in vitro and impedes the tumor growth in vivo. In conclusion, we provide several lines of evidence that the CD164 promotes lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance mediated through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell marker would possibly provide valuable approaches to develop effective therapy for lung cancer, especially for chemoresistant cancers which highly express CD164 using rapamycin as adjuvant therapy.
|
author2 |
James Yi-Hsin Chan |
author_facet |
James Yi-Hsin Chan CHEN, WEI-LIANG 陳韋良 |
author |
CHEN, WEI-LIANG 陳韋良 |
spellingShingle |
CHEN, WEI-LIANG 陳韋良 To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
author_sort |
CHEN, WEI-LIANG |
title |
To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
title_short |
To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
title_full |
To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
title_fullStr |
To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
title_full_unstemmed |
To investigate the role of CD164 in the tumorigenesis and stemness of the lung cancer |
title_sort |
to investigate the role of cd164 in the tumorigenesis and stemness of the lung cancer |
publishDate |
2016 |
url |
http://ndltd.ncl.edu.tw/handle/sva958 |
work_keys_str_mv |
AT chenweiliang toinvestigatetheroleofcd164inthetumorigenesisandstemnessofthelungcancer AT chénwéiliáng toinvestigatetheroleofcd164inthetumorigenesisandstemnessofthelungcancer AT chenweiliang tàntǎocd164yúfèiáizhǒngliúshēngchéngyǔgànxìbāotèxìngzhījiǎosè AT chénwéiliáng tàntǎocd164yúfèiáizhǒngliúshēngchéngyǔgànxìbāotèxìngzhījiǎosè |
_version_ |
1719141817119670272 |