J Exp Clin Cancer Res. 2015 Aug 13;34(1):82. doi: 10.1186/s13046-015-0200-3.

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model.

Pessina A¹, Leonetti C², Artuso S², Benetti A³, Dessy E⁴, Pascucci L⁵, Passeri D⁶, Orlandi A⁶, Berenzi A³, Bonomi A⁷, Coccè V⁷, Ceserani V⁸, Ferri A⁸,Dossena M⁸, Mazzuca P⁹, Ciusani E¹⁰, Ceccarelli P⁵, Caruso A⁹, Portolani N¹¹, Sisto F⁷, Parati E⁸, Alessandri G⁸.

Abstract

BACKGROUND:

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth.

METHODS:

Murine mesenchymal stromal cells were loaded with Paclitaxel (Dr-MCsPTX) according to a standardized procedure and their ability to inhibit the growth of a murine B16 melanoma was verified by in vitro assays. The anti-metastatic activity of Dr-MCsPTX was then studied in mice injected i.v. with B16 melanoma cells that produced lung metastatic nodules. Lung nodules were counted under a dissecting stereomicroscope and metastasis investigated by histological analysis.

RESULTS:

We found that three i.v. injections of Dr-MCsPTX on day 5, 10 and 15 after tumor injection almost completely abolished B16 lung metastasis. Dr-MCsPTX arrested into lung by interacting with endothelium and migrate toward cancer nodule through a complex mechanism involving primarily mouse lung stromal cells (mL-StCs) and SDF-1/CXCR4/CXCR7 axis.

CONCLUSIONS:

Our results show for the first time that Dr-MCsPTX are very effective to inhibit lung metastasis formation. Actually, a cure for lung metastasis in humans is mostly unlikely and we do not know whether a therapy combining engineered MSCs and Dr-MCs may work synergistically. However, we think that our approach using Dr-MCs loaded with PTX may represent a new valid and additive therapeutic tool to fight lung metastases and, perhaps, primary lung cancers in human.