Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis.

Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Research Abstract Details 

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Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Abstract Text:

Juneth J Partridge,Mark A Madsen,Veronica C Ardi,Thales Papagiannakopoulos,Tatyana A Kupriyanova,James P Quigley,Elena I Deryugina,Juneth J Partridge,Mark A Madsen,Veronica C Ardi,Thales Papagiannakopoulos,Tatyana A Kupriyanova,James P Quigley,Elena I Deryugina,Juneth J Partridge,Mark A Madsen,Veronica C Ardi,Thales Papagiannakopoulos,Tatyana A Kupriyanova,James P Quigley,Elena I Deryugina,

The role of tumor-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in cancer cell dissemination was analyzed by employing two variants of human HT-1080 fibrosarcoma, HT-hi/diss and HT-lo/diss, which differ by 50-100-fold in their ability to intravasate and metastasize in the chick embryo. HT-hi/diss and HT-lo/diss were compared by quantitative reverse transcription-PCR and Western blot analyses for mRNA and protein expression of nine MMPs (MMP-1, -2, -3, -7, -8, -9, -10, -13, and -14) and three TIMPs (TIMP-1, -2, and -3) in cultured cells in vitro and in primary tumors in vivo. MMP-1 and MMP-9 were more abundant in the HT-hi/diss variant, both in cultures and in tumors, whereas the HT-lo/diss variant consistently expressed higher levels of MMP-2, TIMP-1, and TIMP-2. Small interfering RNA-mediated down-regulation of MMP-2 and TIMP-2 increased intravasation of HT-lo/diss cells. Coordinately, treatment of the developing HT-hi/diss tumors with recombinant TIMP-1 and TIMP-2 significantly reduced HT-hi/diss cell intravasation. However, a substantial increase of HT-hi/diss dissemination was observed upon small interfering RNA-mediated down-regulation of three secreted MMPs, including the interstitial collagenase MMP-1 and the two gelatinases, MMP-2 and MMP-9, but not the membrane-tethered MMP-14. The addition of recombinant pro-MMP-9 protein to the HT-hi/diss tumors reversed the increased intravasation of HT-hi/diss cells, in which MMP-9 was stably down-regulated by short hairpin RNA interference. This rescue did not occur if the pro-MMP-9 was stoichiometrically complexed with TIMP-1, pointing to a direct role of the MMP-9 enzyme in regulation of HT-hi/diss intravasation. Collectively, these findings demonstrate that tumor-derived MMPs may have protective functions in cancer cell intravasation, i.e. not promoting but rather catalytically interfering with the early stages of cancer dissemination.

Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Publishing Authors By Initials

JJ Partridge,MA Madsen,VC Ardi,T Papagiannakopoulos,TA Kupriyanova,JP Quigley,EI Deryugina,JJ Partridge,MA Madsen,VC Ardi,T Papagiannakopoulos,TA Kupriyanova,JP Quigley,EI Deryugina,JJ Partridge,MA Madsen,VC Ardi,T Papagiannakopoulos,TA Kupriyanova,JP Quigley,EI Deryugina,

For similar proteins: tissue inhibitor of metalloproteinases research abstracts see: proteins: tissue inhibitor of metalloproteinases research

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Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 35964-77

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 25

MONTH: 09

YEAR: 2007

Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Keywords Mesh Terms:

KEYWORDS: Tissue Inhibitor of Metalloproteinases

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis. Information

Substance Name: Matrix Metalloproteinases

Registry Number: EC 3.4.24.-

Grant and Affiliation Information for Functional analysis of matrix metalloproteinases and tissue inhibitors of metalloproteinases differentially expressed by variants of human HT-1080 fibrosarcoma exhibiting high and low levels of intravasation and metastasis.

AFFILIATION: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: T32HL07195

ACRONYM: HL

MEDLINETA: J Biol Chem

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