Premium
Involvement of MMP‐2 in Transendothelial Migration of Invasive Breast Cancer Cells
Author(s) -
KARGOZARAN HAMED,
BRESLIN JEROME W.,
WATSON KATHERINE D.,
YUAN SARAH Y.,
WU MACK H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb12-a
Subject(s) - extravasation , basement membrane , matrix metalloproteinase , metastasis , cancer cell , extracellular matrix , cancer , cell migration , cancer research , chemistry , cell , pathology , microbiology and biotechnology , medicine , biology , biochemistry
Invasive cancer cells are believed to utilize Metalloproteinases (MMPs) to degrade the extracellular matrix and basement membrane during metastasis. However, the role for MMPs in metastatic extravasation is not established. We tested the hypothesis that MMP‐2 facilitates cancer cell migration across the endothelium and basement membrane. We analyzed migration of MDA‐MB‐231 breast cancer cells across human lung microvascular endothelial cell (HLMEC) monolayers grown on basement membrane‐coated Transwell inserts (8 μm pore). Expression of MMP‐2 was specifically inhibited in MDA‐MB‐231 cells using siRNA. A non‐targeting RNA sequence served as control. Immunolotting and zymography were used to assess MMP protein expression and activity, respectively. Our data show that diminished expression of MMP‐2 in MDA‐MB‐231 cells significantly decreases their migration through HLMEC‐coated membranes and membranes without HLMEC, compared to control. This suggests a role for MMP‐2 in the invasive behavior of metastatic cancer cells as well as involvement of MMP‐2 in the extravasation of cancer cells during metastasis. Supported by NIH grants R01 HL73324, R01 HL61507, R01 HL70752, and F32 HL76079.