Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.

Valentina Coccè,Eugenio Parati,Francesco Petrella,Aldo Giannì,Silvia La Monica,Giampietro Farronato,Lisa Flammini,Angela Falco,Costanza Annamaria Lagrasta,Mara Bonelli,Augusto Pessina,Caterina Frati,Angela Marcianti,Lorenzo Spaggiari,Roberta Alfieri,Francesca Paino,Denise Madeddu,Giulio Alessandri,Daniela Lisini

doi:10.3390/cells10061427

Abstract

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. Results: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. Conclusions: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.

Highlights

Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to widespread asbestos exposure [1]
The lysates (MSCs LYS) and the conditioned medium (MSCs conditioned media (CM)) of mesenchymal stromal cells (MSCs) obtained from three different donors have been tested concerning the proliferation of MSTO-211H, NCI-H2452 and NCI-H2052 mesothelioma cell lines
Both the lysates and the conditioned medium produced a significant inhibition of the proliferation of mesothelioma cell lines (Figure 1A,B)

Summary

Introduction

Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to widespread asbestos exposure [1]. Many reports suggest that MSCs and/or MSCs-derived secretome can exert antitumor activity against many different types of cancers such as leukemia, prostate carcinoma, colon carcinoma, and breast cancer, both in vitro and in vivo models [9,10,11,12]. To explain these anticancer effects, different mechanisms have been investigated such as apoptosis induction due to Tumor Necrosis Factor-Related Apoptosis-Inducing. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy

Objectives

Methods

Results