TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis

Mumtaz V Rojiani, Sampa Ghoshal-Gupta, Ammar Kutiyanawalla, Sunil Mathur, Amyn Mohammed Rojiani

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition ofmatrix metalloproteinase activity, activation of proYmatrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1Yoverexpressing vector (HB-6 and HB-1). Tumors resulting from the implantation of parental cell lines and transfected HB-1 cells into the brains of nude mice had a typical carcinoma profile, but human TIMP-1Yoverexpressing tumors showed enhanced tumor kinetics and focally more infiltrative features; vessel density assessed with anti-CD31 immunohistochemistry was also greater within HB-1 tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines and empty vector clones were observed in endothelial cell assays. Anchorage-independent growth and invasion through Matrigel were also increased in TIMP- 1Yoverexpressing cells. Together, these results indicate tumorpromoting functions of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and invasive behavior. Although matrix metalloproteinase inhibition has been the traditionally identified function of TIMP-1, matrix metalloproteinaseYindependent interactions may contribute to the growth of metastatic carcinomas in the brain.

Original languageEnglish (US)
Pages (from-to)293-304
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume74
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Neoplasm Metastasis
Carcinoma
Lung
Brain
Neoplasms
Metalloproteases
Cell Line
Growth
Matrix Metalloproteinases
Nude Mice
Endothelial Cells
Clone Cells
Immunohistochemistry
Cell Proliferation
Apoptosis
Messenger RNA

Keywords

  • Adenocarcinoma
  • Brain
  • Extracellular matrix
  • Matrix metalloproteinase
  • Metastasis
  • Tissue inhibitors of matrix metalloproteinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis. / Rojiani, Mumtaz V; Ghoshal-Gupta, Sampa; Kutiyanawalla, Ammar; Mathur, Sunil; Rojiani, Amyn Mohammed.

In: Journal of Neuropathology and Experimental Neurology, Vol. 74, No. 4, 01.01.2015, p. 293-304.

Research output: Contribution to journalArticle

@article{e034541551244fb79dd41d270ffa8729,
title = "TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis",
abstract = "Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition ofmatrix metalloproteinase activity, activation of proYmatrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1Yoverexpressing vector (HB-6 and HB-1). Tumors resulting from the implantation of parental cell lines and transfected HB-1 cells into the brains of nude mice had a typical carcinoma profile, but human TIMP-1Yoverexpressing tumors showed enhanced tumor kinetics and focally more infiltrative features; vessel density assessed with anti-CD31 immunohistochemistry was also greater within HB-1 tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines and empty vector clones were observed in endothelial cell assays. Anchorage-independent growth and invasion through Matrigel were also increased in TIMP- 1Yoverexpressing cells. Together, these results indicate tumorpromoting functions of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and invasive behavior. Although matrix metalloproteinase inhibition has been the traditionally identified function of TIMP-1, matrix metalloproteinaseYindependent interactions may contribute to the growth of metastatic carcinomas in the brain.",
keywords = "Adenocarcinoma, Brain, Extracellular matrix, Matrix metalloproteinase, Metastasis, Tissue inhibitors of matrix metalloproteinase",
author = "Rojiani, {Mumtaz V} and Sampa Ghoshal-Gupta and Ammar Kutiyanawalla and Sunil Mathur and Rojiani, {Amyn Mohammed}",
year = "2015",
month = "1",
day = "1",
doi = "10.1097/NEN.0000000000000175",
language = "English (US)",
volume = "74",
pages = "293--304",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis

AU - Rojiani, Mumtaz V

AU - Ghoshal-Gupta, Sampa

AU - Kutiyanawalla, Ammar

AU - Mathur, Sunil

AU - Rojiani, Amyn Mohammed

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition ofmatrix metalloproteinase activity, activation of proYmatrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1Yoverexpressing vector (HB-6 and HB-1). Tumors resulting from the implantation of parental cell lines and transfected HB-1 cells into the brains of nude mice had a typical carcinoma profile, but human TIMP-1Yoverexpressing tumors showed enhanced tumor kinetics and focally more infiltrative features; vessel density assessed with anti-CD31 immunohistochemistry was also greater within HB-1 tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines and empty vector clones were observed in endothelial cell assays. Anchorage-independent growth and invasion through Matrigel were also increased in TIMP- 1Yoverexpressing cells. Together, these results indicate tumorpromoting functions of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and invasive behavior. Although matrix metalloproteinase inhibition has been the traditionally identified function of TIMP-1, matrix metalloproteinaseYindependent interactions may contribute to the growth of metastatic carcinomas in the brain.

AB - Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition ofmatrix metalloproteinase activity, activation of proYmatrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1Yoverexpressing vector (HB-6 and HB-1). Tumors resulting from the implantation of parental cell lines and transfected HB-1 cells into the brains of nude mice had a typical carcinoma profile, but human TIMP-1Yoverexpressing tumors showed enhanced tumor kinetics and focally more infiltrative features; vessel density assessed with anti-CD31 immunohistochemistry was also greater within HB-1 tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines and empty vector clones were observed in endothelial cell assays. Anchorage-independent growth and invasion through Matrigel were also increased in TIMP- 1Yoverexpressing cells. Together, these results indicate tumorpromoting functions of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and invasive behavior. Although matrix metalloproteinase inhibition has been the traditionally identified function of TIMP-1, matrix metalloproteinaseYindependent interactions may contribute to the growth of metastatic carcinomas in the brain.

KW - Adenocarcinoma

KW - Brain

KW - Extracellular matrix

KW - Matrix metalloproteinase

KW - Metastasis

KW - Tissue inhibitors of matrix metalloproteinase

UR - http://www.scopus.com/inward/record.url?scp=84925876723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925876723&partnerID=8YFLogxK

U2 - 10.1097/NEN.0000000000000175

DO - 10.1097/NEN.0000000000000175

M3 - Article

C2 - 25756591

AN - SCOPUS:84925876723

VL - 74

SP - 293

EP - 304

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 4

ER -