Τίτλος:
Beneficial Impact of CCL2 and CCL12 Neutralization on Experimental
Malignant Pleural Effusion
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Using genetic interventions, we previously determined that C-C motif
chemokine ligand 2 (CCL2) promotes malignant pleural effusion (MPE)
formation in mice. Here we conducted preclinical studies aimed at
assessing the specific therapeutic potential of antibody-mediated CCL2
blockade against MPE. For this, murine MPEs or skin tumors were
generated in C57BL/6 mice by intrapleural or subcutaneous delivery of
lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung
adenocarcinoma cells (A549) were used to induce MPEs in severe combined
immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2
and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50
mg/kg every three days. We found that high doses of CCL2/12 neutralizing
antibody treatment (50 mg/kg) were required to limit MPE formation by
LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE
development by LLC cells. Combined CCL2 and CCL12 neutralization was
also effective against MC38-induced MPE and prolonged the survival of
mice in both syngeneic models. Mouse-specific CCL2-blockade limited
A549-caused xenogeneic MPE, indicating that host-derived CCL2 also
contributes to MPE precipitation in mice. The impact of CCL2/12
antagonism was associated with inhibition of immune and vascular
MPE-related phenomena, such as inflammation, new blood vessel assembly
and plasma extravasation into the pleural space. We conclude that CCL2
and CCL12 blockade are effective against experimental MPE induced by
murine and human adenocarcinoma in mice. These results suggest that
CCL2-targeted therapies may hold promise for future use against human
MPE.
Συγγραφείς:
Marazioti, Antonia
Kairi, Chrysoula A.
Spella, Magda and
Giannou, Anastasios D.
Magkouta, Sophia
Giopanou, Ioanna and
Papaleonidopoulos, Vassilios
Kalomenidis, Ioannis
Snyder, Linda
A.
Kardamakis, Dimitrios
Stathopoulos, Georgios T.
Εκδότης:
Public Library of Science
DOI:
10.1371/journal.pone.0071207
