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

Augusto Pessina, Carlo Leonetti, Simona Artuso, Anna Benetti, Enrico Dessy, Luisa Pascucci, Daniela Passeri, Augusto Orlandi, Angiola Berenzi, Arianna Bonomi, Valentina Coccè, Valentina Ceserani, Anna Ferri, Marta Dossena, Pietro Mazzuca, Emilio Ciusani, Piero Ceccarelli, Arnaldo Caruso, Nazario Portolani, Francesca SistoEugenio Parati, Giulio Alessandri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number200
JournalJournal of Experimental and Clinical Cancer Research
Volume34
Issue number1
DOIs
Publication statusPublished - Aug 13 2015

Fingerprint

Neoplasm Metastasis
Lung
Mesenchymal Stromal Cells
Pharmaceutical Preparations
Experimental Melanomas
Neoplasms
Therapeutics
Injections
Stromal Cells
Growth
Paclitaxel
Endothelium
Lung Neoplasms
In Vitro Techniques

Keywords

  • B16 melanoma
  • Drug-delivery
  • Lung metastasis
  • Mesenchymal stromal cells
  • Paclitaxel
  • SDF-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model. / Pessina, Augusto; Leonetti, Carlo; Artuso, Simona; Benetti, Anna; Dessy, Enrico; Pascucci, Luisa; Passeri, Daniela; Orlandi, Augusto; Berenzi, Angiola; Bonomi, Arianna; Coccè, Valentina; Ceserani, Valentina; Ferri, Anna; Dossena, Marta; Mazzuca, Pietro; Ciusani, Emilio; Ceccarelli, Piero; Caruso, Arnaldo; Portolani, Nazario; Sisto, Francesca; Parati, Eugenio; Alessandri, Giulio.

In: Journal of Experimental and Clinical Cancer Research, Vol. 34, No. 1, 200, 13.08.2015.

Research output: Contribution to journalArticle

Pessina, A, Leonetti, C, Artuso, S, Benetti, A, Dessy, E, Pascucci, L, Passeri, D, Orlandi, A, Berenzi, A, Bonomi, A, Coccè, V, Ceserani, V, Ferri, A, Dossena, M, Mazzuca, P, Ciusani, E, Ceccarelli, P, Caruso, A, Portolani, N, Sisto, F, Parati, E & Alessandri, G 2015, 'Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model', Journal of Experimental and Clinical Cancer Research, vol. 34, no. 1, 200. https://doi.org/10.1186/s13046-015-0200-3
Pessina, Augusto ; Leonetti, Carlo ; Artuso, Simona ; Benetti, Anna ; Dessy, Enrico ; Pascucci, Luisa ; Passeri, Daniela ; Orlandi, Augusto ; Berenzi, Angiola ; Bonomi, Arianna ; Coccè, Valentina ; Ceserani, Valentina ; Ferri, Anna ; Dossena, Marta ; Mazzuca, Pietro ; Ciusani, Emilio ; Ceccarelli, Piero ; Caruso, Arnaldo ; Portolani, Nazario ; Sisto, Francesca ; Parati, Eugenio ; Alessandri, Giulio. / Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model. In: Journal of Experimental and Clinical Cancer Research. 2015 ; Vol. 34, No. 1.
@article{1aa81a9f928e4b01930bb875d76d1f41,
title = "Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model",
abstract = "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.",
keywords = "B16 melanoma, Drug-delivery, Lung metastasis, Mesenchymal stromal cells, Paclitaxel, SDF-1",
author = "Augusto Pessina and Carlo Leonetti and Simona Artuso and Anna Benetti and Enrico Dessy and Luisa Pascucci and Daniela Passeri and Augusto Orlandi and Angiola Berenzi and Arianna Bonomi and Valentina Cocc{\`e} and Valentina Ceserani and Anna Ferri and Marta Dossena and Pietro Mazzuca and Emilio Ciusani and Piero Ceccarelli and Arnaldo Caruso and Nazario Portolani and Francesca Sisto and Eugenio Parati and Giulio Alessandri",
year = "2015",
month = "8",
day = "13",
doi = "10.1186/s13046-015-0200-3",
language = "English",
volume = "34",
journal = "Journal of Experimental and Clinical Cancer Research",
issn = "0392-9078",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

AU - Pessina, Augusto

AU - Leonetti, Carlo

AU - Artuso, Simona

AU - Benetti, Anna

AU - Dessy, Enrico

AU - Pascucci, Luisa

AU - Passeri, Daniela

AU - Orlandi, Augusto

AU - Berenzi, Angiola

AU - Bonomi, Arianna

AU - Coccè, Valentina

AU - Ceserani, Valentina

AU - Ferri, Anna

AU - Dossena, Marta

AU - Mazzuca, Pietro

AU - Ciusani, Emilio

AU - Ceccarelli, Piero

AU - Caruso, Arnaldo

AU - Portolani, Nazario

AU - Sisto, Francesca

AU - Parati, Eugenio

AU - Alessandri, Giulio

PY - 2015/8/13

Y1 - 2015/8/13

N2 - 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.

AB - 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.

KW - B16 melanoma

KW - Drug-delivery

KW - Lung metastasis

KW - Mesenchymal stromal cells

KW - Paclitaxel

KW - SDF-1

UR - http://www.scopus.com/inward/record.url?scp=84938945059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938945059&partnerID=8YFLogxK

U2 - 10.1186/s13046-015-0200-3

DO - 10.1186/s13046-015-0200-3

M3 - Article

AN - SCOPUS:84938945059

VL - 34

JO - Journal of Experimental and Clinical Cancer Research

JF - Journal of Experimental and Clinical Cancer Research

SN - 0392-9078

IS - 1

M1 - 200

ER -