Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation

Shih Hsun Chen, Wei Chien Hung, Pu Wang, Colin Paul, K Konstantopoulos

Research output: Contribution to journalArticle

Abstract

Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. Using sophisticated bioengineering and molecular biology tools, we report that the binding of MSLN to MUC16 markedly enhances PC cell motility and invasion via the selective induction of matrix metalloproteinase (MMP)-7. MSLN-mediated MMP-7 upregulation in MUC16-expressing PC cells occurs via a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated PC motility and invasion. These findings provide a novel perspective on the enhanced invasive potential associated with MSLN and MUC16 co-overexpression, and the mechanism underlying MMP-7 activation in PC invasion and metastasis.

Original languageEnglish (US)
Article number1870
JournalScientific Reports
Volume3
DOIs
StatePublished - 2013

Fingerprint

CA-125 Antigen
Matrix Metalloproteinase 7
Pancreatic Neoplasms
Cell Movement
Neoplasms
Bioengineering
p38 Mitogen-Activated Protein Kinases
mesothelin
Molecular Biology
Up-Regulation
Biomarkers
Neoplasm Metastasis

ASJC Scopus subject areas

  • General

Cite this

Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. / Chen, Shih Hsun; Hung, Wei Chien; Wang, Pu; Paul, Colin; Konstantopoulos, K.

In: Scientific Reports, Vol. 3, 1870, 2013.

Research output: Contribution to journalArticle

@article{0886210ff0d248fc90ed3858482968ea,
title = "Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation",
abstract = "Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. Using sophisticated bioengineering and molecular biology tools, we report that the binding of MSLN to MUC16 markedly enhances PC cell motility and invasion via the selective induction of matrix metalloproteinase (MMP)-7. MSLN-mediated MMP-7 upregulation in MUC16-expressing PC cells occurs via a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated PC motility and invasion. These findings provide a novel perspective on the enhanced invasive potential associated with MSLN and MUC16 co-overexpression, and the mechanism underlying MMP-7 activation in PC invasion and metastasis.",
author = "Chen, {Shih Hsun} and Hung, {Wei Chien} and Pu Wang and Colin Paul and K Konstantopoulos",
year = "2013",
doi = "10.1038/srep01870",
language = "English (US)",
volume = "3",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Mesothelin binding to CA125/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation

AU - Chen, Shih Hsun

AU - Hung, Wei Chien

AU - Wang, Pu

AU - Paul, Colin

AU - Konstantopoulos, K

PY - 2013

Y1 - 2013

N2 - Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. Using sophisticated bioengineering and molecular biology tools, we report that the binding of MSLN to MUC16 markedly enhances PC cell motility and invasion via the selective induction of matrix metalloproteinase (MMP)-7. MSLN-mediated MMP-7 upregulation in MUC16-expressing PC cells occurs via a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated PC motility and invasion. These findings provide a novel perspective on the enhanced invasive potential associated with MSLN and MUC16 co-overexpression, and the mechanism underlying MMP-7 activation in PC invasion and metastasis.

AB - Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. Using sophisticated bioengineering and molecular biology tools, we report that the binding of MSLN to MUC16 markedly enhances PC cell motility and invasion via the selective induction of matrix metalloproteinase (MMP)-7. MSLN-mediated MMP-7 upregulation in MUC16-expressing PC cells occurs via a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated PC motility and invasion. These findings provide a novel perspective on the enhanced invasive potential associated with MSLN and MUC16 co-overexpression, and the mechanism underlying MMP-7 activation in PC invasion and metastasis.

UR - http://www.scopus.com/inward/record.url?scp=84878623168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878623168&partnerID=8YFLogxK

U2 - 10.1038/srep01870

DO - 10.1038/srep01870

M3 - Article

C2 - 23694968

AN - SCOPUS:84878623168

VL - 3

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 1870

ER -