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Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy

Authors
 Sun-Jin Kim ; Jang-Seong Kim ; Isaiah J. Fidler ; Mien-Chie Hung ; Gordon B.Mills ; Dominic Fan ; Krishnakumar Balasubramanian ; Zhang Weihua ; Seung-Wook Kim ; Junqin He ; Marva Maya ; Robert R. Langley ; Qingtang Lin ; Ju-Seog Lee ; Eun Sung Park 
Citation
 Neoplasia, Vol.13(3) : 286~298, 2011 
Journal Title
 Neoplasia 
ISSN
 1522-8002 
Issue Date
2011
Abstract
In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts) led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/92918
DOI
10.1593/neo.11112
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Institute for Medical Convergence
Yonsei Authors
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