Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth

Pamarthi M. Mohan; Shravan K. Chintala; Sanjeeva Mohanam; Candece L. Gladson; Eui So Kim; Ziya L. Gokaslan; Sajani S. Lakka; Jack A. Roth; Bingliang Fang; Raymond Sawaya; Athanassios P. Kyritsis; Jasti S. Rao

Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth

Pamarthi M. Mohan, Shravan K. Chintala, Sanjeeva Mohanam, Candece L. Gladson, Eui So Kim, Ziya L. Gokaslan, Sajani S. Lakka, Jack A. Roth, Bingliang Fang, Raymond Sawaya, Athanassios P. Kyritsis, Jasti S. Rao

School of Medicine

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

The urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors. We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. s.c. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR- infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established s.c. U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.

Original language	English (US)
Pages (from-to)	3369-3373
Number of pages	5
Journal	Cancer Research
Volume	59
Issue number	14
State	Published - Jul 15 1999

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth",

abstract = "The urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors. We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. s.c. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR- infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established s.c. U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.",

author = "Mohan, {Pamarthi M.} and Chintala, {Shravan K.} and Sanjeeva Mohanam and Gladson, {Candece L.} and Kim, {Eui So} and Gokaslan, {Ziya L.} and Lakka, {Sajani S.} and Roth, {Jack A.} and Bingliang Fang and Raymond Sawaya and Kyritsis, {Athanassios P.} and Rao, {Jasti S.}",

year = "1999",

month = jul,

day = "15",

language = "English (US)",

volume = "59",

pages = "3369--3373",

journal = "Cancer Research",

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T1 - Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth

AU - Mohan, Pamarthi M.

AU - Chintala, Shravan K.

AU - Mohanam, Sanjeeva

AU - Gladson, Candece L.

AU - Kim, Eui So

AU - Gokaslan, Ziya L.

AU - Lakka, Sajani S.

AU - Roth, Jack A.

AU - Fang, Bingliang

AU - Sawaya, Raymond

AU - Kyritsis, Athanassios P.

AU - Rao, Jasti S.

PY - 1999/7/15

Y1 - 1999/7/15

N2 - The urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors. We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. s.c. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR- infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established s.c. U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.

AB - The urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors. We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. s.c. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR- infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established s.c. U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.

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AN - SCOPUS:0033565613

SN - 0008-5472

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JO - Cancer Research

JF - Cancer Research

IS - 14

ER -

Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth

Abstract

ASJC Scopus subject areas

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