Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype

Andy Shau Bin Chou, Hung Chang Chen, Chia Rui Li, Chin Hsuan Hsieh, Lai Lei Ting, Shuen Kuei Liao

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10 6 cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalCancer Biotherapy and Radiopharmaceuticals
Volume26
Issue number4
DOIs
Publication statusPublished - Aug 1 2011

Fingerprint

SCID Mice
Subcutaneous Injections
Phenotype
Neoplasms
Bone Marrow
Interferons
Cell Differentiation
Heterologous Transplantation
Injections
Keratins
Nasopharyngeal carcinoma
Heterografts
Bone Marrow Cells
Necrosis
Observation
Neoplasm Metastasis
Growth
Genes

Keywords

  • bone marrow metastases
  • IFN-γ
  • nasopharyngeal carcinoma
  • tumor dormancy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype. / Chou, Andy Shau Bin; Chen, Hung Chang; Li, Chia Rui; Hsieh, Chin Hsuan; Ting, Lai Lei; Liao, Shuen Kuei.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 26, No. 4, 01.08.2011, p. 417-426.

Research output: Contribution to journalArticle

@article{459d31776c5c4f4081a718b2042adffe,
title = "Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype",
abstract = "The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10 6 cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.",
keywords = "bone marrow metastases, IFN-γ, nasopharyngeal carcinoma, tumor dormancy",
author = "Chou, {Andy Shau Bin} and Chen, {Hung Chang} and Li, {Chia Rui} and Hsieh, {Chin Hsuan} and Ting, {Lai Lei} and Liao, {Shuen Kuei}",
year = "2011",
month = "8",
day = "1",
doi = "10.1089/cbr.2011.0958",
language = "English",
volume = "26",
pages = "417--426",
journal = "Cancer Biotherapy and Radiopharmaceuticals",
issn = "1084-9785",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype

AU - Chou, Andy Shau Bin

AU - Chen, Hung Chang

AU - Li, Chia Rui

AU - Hsieh, Chin Hsuan

AU - Ting, Lai Lei

AU - Liao, Shuen Kuei

PY - 2011/8/1

Y1 - 2011/8/1

N2 - The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10 6 cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.

AB - The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10 6 cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.

KW - bone marrow metastases

KW - IFN-γ

KW - nasopharyngeal carcinoma

KW - tumor dormancy

UR - http://www.scopus.com/inward/record.url?scp=80051714085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051714085&partnerID=8YFLogxK

U2 - 10.1089/cbr.2011.0958

DO - 10.1089/cbr.2011.0958

M3 - Article

C2 - 21810020

AN - SCOPUS:80051714085

VL - 26

SP - 417

EP - 426

JO - Cancer Biotherapy and Radiopharmaceuticals

JF - Cancer Biotherapy and Radiopharmaceuticals

SN - 1084-9785

IS - 4

ER -