2 research outputs found
Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126
Tumor suppressor microRNA-126 (miR-126)
is often down-regulated
in cancer cells, and its overexpression is found to inhibit cancer
metastasis. To elucidate the mechanism of tumor suppression by miR-126,
we analyzed the proteomic response to miR-126 overexpression in the
human metastatic breast cancer cell line MDA-MB-231. To acquire quantitative,
time-resolved information, we combined two complementary proteomic
methods, BONCAT and SILAC. We discovered a new direct target of miR-126:
CD97, a pro-metastatic G-protein-coupled receptor (GPCR) that has
been reported to promote tumor cell invasion, endothelial cell migration,
and tumor angiogenesis. This discovery establishes a link between
down-regulation of miR-126 and overexpression of CD97 in cancer and
provides new mechanistic insight into the role of miR-126 in inhibiting
both cell-autonomous and non-cell-autonomous cancer progression
Synthesis and Cell Adhesive Properties of Linear and Cyclic RGD Functionalized Polynorbornene Thin Films
Described herein is the efficient synthesis and evaluation
of bioactive
arginine-glycine-aspartic acid (RGD) functionalized polynorbornene-based
materials for cell adhesion and spreading. Polynorbornenes containing
either linear or cyclic RGD peptides were synthesized by ring-opening
metathesis polymerization (ROMP) using the well-defined ruthenium
initiator [(H<sub>2</sub>IMes)Â(pyr)<sub>2</sub>(Cl)<sub>2</sub>Ruî—»CHPh].
The random copolymerization of three separate norbornene monomers
allowed for the incorporation of water-soluble polyethylene glycol
(PEG) moieties, RGD cell recognition motifs, and primary amines for
postpolymerization cross-linking. Following polymer synthesis, thin-film
hydrogels were formed by cross-linking with bisÂ(sulfosuccinimidyl)
suberate (BS<sup>3</sup>), and the ability of these materials to support
human umbilical vein endothelial cell (HUVEC) adhesion and spreading
was evaluated and quantified. When compared to control polymers containing
either no peptide or a scrambled RDG peptide, polymers with linear
or cyclic RGD at varying concentrations displayed excellent cell adhesive
properties in both serum-supplemented and serum-free media. Polymers
with cyclic RGD side chains maintained cell adhesion and exhibited
comparable integrin binding at a 100-fold lower concentration than
those carrying linear RGD peptides. The precise control of monomer
incorporation enabled by ROMP allows for quantification of the impact
of RGD structure and concentration on cell adhesion and spreading.
The results presented here will serve to guide future efforts for
the design of RGD functionalized materials with applications in surgery,
tissue engineering, and regenerative medicine