Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC

Shanna Arnold, Emilia Mira, Sabeeha Muneer, Grzegorz Korpanty, Adam W. Beck, Shane E. Holloway, Santos Mañes, Rolf A. Brekken

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Pancreatic adenocarcinoma is characterized by desmoplasia, local invasion, and metastasis. These features are regulated in part by MMP9 and SPARC. To explore the interaction of SPARC and MMP9 in cancer, we first established orthotopic pancreatic tumors in SPARC-null and wild-type mice with the murine pancreatic adenocarcinoma cell line, PAN02. MMP9 expression was higher in tumors from wild-type compared to SPARC-null mice. Coincident with lower MMP9 expression, tumors grown in SPARC-null mice were significantly larger, had decreased ECM deposition and reduced microvessel density compared to wild-type controls. In addition, metastasis was enhanced in the absence of host SPARC. Therefore, we next analyzed the orthotopic tumor growth of PAN02 cells transduced with MMP9 or a control empty vector. Forced expression of MMP9 by the PAN02 cells resulted in larger tumors in both wild-type and SPARC-null animals compared to empty vector controls and further diminished ECM deposition. Importantly, forced expression of MMP9 within the tumor reversed the decrease in angiogenesis and abrogated the metastatic potential displayed by control tumors grown in SPARC-null mice. Finally, contrary to the in vivo results, MMP9 increased cell migration in vitro, which was blocked by the addition of SPARC. These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)860-873
Number of pages14
JournalExperimental Biology and Medicine
Volume233
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Tumors
Neoplasm Metastasis
Military electronic countermeasures
Neoplasms
Adenocarcinoma
Microvessels
Animals
Cell Movement
Cells
Cell Line
Growth

Keywords

  • ECM; pancreatic; metastasis
  • MMP9
  • SPARC
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. / Arnold, Shanna; Mira, Emilia; Muneer, Sabeeha; Korpanty, Grzegorz; Beck, Adam W.; Holloway, Shane E.; Mañes, Santos; Brekken, Rolf A.

In: Experimental Biology and Medicine, Vol. 233, No. 7, 07.2008, p. 860-873.

Research output: Contribution to journalArticle

Arnold, Shanna ; Mira, Emilia ; Muneer, Sabeeha ; Korpanty, Grzegorz ; Beck, Adam W. ; Holloway, Shane E. ; Mañes, Santos ; Brekken, Rolf A. / Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. In: Experimental Biology and Medicine. 2008 ; Vol. 233, No. 7. pp. 860-873.
@article{255020e454a8452b8713024c926bfd0d,
title = "Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC",
abstract = "Pancreatic adenocarcinoma is characterized by desmoplasia, local invasion, and metastasis. These features are regulated in part by MMP9 and SPARC. To explore the interaction of SPARC and MMP9 in cancer, we first established orthotopic pancreatic tumors in SPARC-null and wild-type mice with the murine pancreatic adenocarcinoma cell line, PAN02. MMP9 expression was higher in tumors from wild-type compared to SPARC-null mice. Coincident with lower MMP9 expression, tumors grown in SPARC-null mice were significantly larger, had decreased ECM deposition and reduced microvessel density compared to wild-type controls. In addition, metastasis was enhanced in the absence of host SPARC. Therefore, we next analyzed the orthotopic tumor growth of PAN02 cells transduced with MMP9 or a control empty vector. Forced expression of MMP9 by the PAN02 cells resulted in larger tumors in both wild-type and SPARC-null animals compared to empty vector controls and further diminished ECM deposition. Importantly, forced expression of MMP9 within the tumor reversed the decrease in angiogenesis and abrogated the metastatic potential displayed by control tumors grown in SPARC-null mice. Finally, contrary to the in vivo results, MMP9 increased cell migration in vitro, which was blocked by the addition of SPARC. These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis.",
keywords = "ECM; pancreatic; metastasis, MMP9, SPARC, Tumor microenvironment",
author = "Shanna Arnold and Emilia Mira and Sabeeha Muneer and Grzegorz Korpanty and Beck, {Adam W.} and Holloway, {Shane E.} and Santos Ma{\~n}es and Brekken, {Rolf A.}",
year = "2008",
month = "7",
doi = "10.3181/0801-RM-12",
language = "English (US)",
volume = "233",
pages = "860--873",
journal = "Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "7",

}

TY - JOUR

T1 - Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC

AU - Arnold, Shanna

AU - Mira, Emilia

AU - Muneer, Sabeeha

AU - Korpanty, Grzegorz

AU - Beck, Adam W.

AU - Holloway, Shane E.

AU - Mañes, Santos

AU - Brekken, Rolf A.

PY - 2008/7

Y1 - 2008/7

N2 - Pancreatic adenocarcinoma is characterized by desmoplasia, local invasion, and metastasis. These features are regulated in part by MMP9 and SPARC. To explore the interaction of SPARC and MMP9 in cancer, we first established orthotopic pancreatic tumors in SPARC-null and wild-type mice with the murine pancreatic adenocarcinoma cell line, PAN02. MMP9 expression was higher in tumors from wild-type compared to SPARC-null mice. Coincident with lower MMP9 expression, tumors grown in SPARC-null mice were significantly larger, had decreased ECM deposition and reduced microvessel density compared to wild-type controls. In addition, metastasis was enhanced in the absence of host SPARC. Therefore, we next analyzed the orthotopic tumor growth of PAN02 cells transduced with MMP9 or a control empty vector. Forced expression of MMP9 by the PAN02 cells resulted in larger tumors in both wild-type and SPARC-null animals compared to empty vector controls and further diminished ECM deposition. Importantly, forced expression of MMP9 within the tumor reversed the decrease in angiogenesis and abrogated the metastatic potential displayed by control tumors grown in SPARC-null mice. Finally, contrary to the in vivo results, MMP9 increased cell migration in vitro, which was blocked by the addition of SPARC. These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis.

AB - Pancreatic adenocarcinoma is characterized by desmoplasia, local invasion, and metastasis. These features are regulated in part by MMP9 and SPARC. To explore the interaction of SPARC and MMP9 in cancer, we first established orthotopic pancreatic tumors in SPARC-null and wild-type mice with the murine pancreatic adenocarcinoma cell line, PAN02. MMP9 expression was higher in tumors from wild-type compared to SPARC-null mice. Coincident with lower MMP9 expression, tumors grown in SPARC-null mice were significantly larger, had decreased ECM deposition and reduced microvessel density compared to wild-type controls. In addition, metastasis was enhanced in the absence of host SPARC. Therefore, we next analyzed the orthotopic tumor growth of PAN02 cells transduced with MMP9 or a control empty vector. Forced expression of MMP9 by the PAN02 cells resulted in larger tumors in both wild-type and SPARC-null animals compared to empty vector controls and further diminished ECM deposition. Importantly, forced expression of MMP9 within the tumor reversed the decrease in angiogenesis and abrogated the metastatic potential displayed by control tumors grown in SPARC-null mice. Finally, contrary to the in vivo results, MMP9 increased cell migration in vitro, which was blocked by the addition of SPARC. These results suggest that SPARC and MMP9 interact to regulate many stages of tumor progression including ECM deposition, angiogenesis and metastasis.

KW - ECM; pancreatic; metastasis

KW - MMP9

KW - SPARC

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=47749119594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47749119594&partnerID=8YFLogxK

U2 - 10.3181/0801-RM-12

DO - 10.3181/0801-RM-12

M3 - Article

C2 - 18445772

AN - SCOPUS:47749119594

VL - 233

SP - 860

EP - 873

JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

SN - 1535-3702

IS - 7

ER -