MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential

  • Naomi D’souza
  • Jorge Sans Burns
  • Giulia Grisendi
  • Olivia Candini
  • Elena Veronesi
  • Serena Piccinno
  • Edwin M. Horwitz
  • Paolo Paolucci
  • Pierfranco Conte
  • Massimo Dominici
Chapter

Abstract

Mesenchymal stromal/stem cells (MSC) are adult multipotent progenitors with fibroblast-like morphology able to differentiate into adipocytic, osteogenic, chondrogenic, and myogenic lineages. Due to these properties, MSC have been studied and introduced as therapeutics in regenerative medicine. Preliminary studies have also shown a possible involvement of MSC as precursors of cellular elements within tumor microenvironments, in particular tumor-associated fibroblasts (TAF). Among a number of different possible origins, TAF may originate from a pool of circulating progenitors from bone marrow or adipose tissue-derived MSC. There is growing evidence to corroborate that cells immunophenotypically defined as MSC are able to reside as TAF influencing the tumor microenvironment in a potentially bi-phasic and obscure manner: either promoting or inhibiting growth depending on tumor context and MSC sources. Here we focus on relationships between the tumor microenvironment, cancer cells, and MSC, analyzing their diverse ability to influence neoplastic development. Associated activities include MSC homing driven by the secretion of various mediators, differentiation towards TAF phenotypes, and reciprocal interactions with the tumor cells. These are reviewed here with the aim of understanding the biological functions of MSC that can be exploited for innovative cancer therapy.

Graphical Abstract

Keywords

MSC Microenvironment Tumor stroma TAF TRAIL 

Abbreviations

5-FC

5-Fluorocytosine

AAV

Adeno associated viruses

APC

Antigen presenting cells

Ang-1

Angiopoietin 1

bFGF

Basic fibroblast growth factor

BM

Bone marrow

BrdUrd

Bromodeoxyuridine

c-fibronectin

Cellular fibronectin

CSC

Cancer stem cells

CTL

Cytotoxic T Lymphocytes

DC

Dendritic cells

DKK-1

Dickkopf-related protein-1

DL

Death ligand

ECM

Extracellular matrix

EGF

Epidermal growth factor

EMT

Epithelial to mesenchymal transition

EndMT

Endothelial to mesenchymal transition

EPC

Endothelial progenitor cells

ESC

Embryonic stem cell

ET-1

Endothelin-1

ETBR

Endothelin binding receptor

FAK

Focal adhesion kinase

FAP

Fibroblast activation protein

FPRL-1

Formyl peptide receptor like-1

FSP

Fibroblast specific protein

G-CSF

Granulocyte-colony-stimulating factor

GM-CSF

Granulocyte-macrophage-colony-stimulating factor

hAD-MSC

Human adipose-derived mesenchymal stromal/stem cells

hBM-MSC

Human bone marrow-derived mesenchymal stromal/stem cells

HCC

Hepatocarcinoma cancer

HGF

Hepatocyte growth factor

HLA

Human leukocyte antigen

HLA-DR

Human leukocyte antigen and its ligand

hMSC

Human mesenchymal stromal/stem cells

HO-1

Heme oxygenase-1

HSC

Hematopoietic stem cells

IDO

Indolamin 2, 3-dioxygenase

IFN-γ

Interferon-gamma

IGF

Insulin growth factor

IL

Interleukin

LIF

Leukemia inhibitory factor

MCP-1/CCL5

Monocyte chemotactic protein-1

M-CSF

Macrophage-colony-stimulating factor

MDSCs

Myeloid derived suppressor cells

miRNA

microRNA

MMP

Matrix metalloproteinases

MSC

Mesenchymal stromal/stem cells

NF-κB

Nuclear factor-kappa B

NHL

non-Hodgkin lymphoma

NK cells

Natural killer cells

NO

Nitric oxide

NSCLC

Non-small cell lung carcinoma

OI

Osteogenesis imperfecta

PAI-1

Plasminogen activator inhibitor type-1

PAI-2

Plasminogen activator inhibitor type-2

PDGF

Platelet derived growth factor

p-fibronectin

Plasma fibronectin

PGE2

Prostaglandin E2

PIFA

Platinum-induced polyunsaturated fatty acids

PlGF

Placental growth factor

ROS

Reactive oxygen species

SCID

Severe combined immunodeficieny

SDF-1/CXCL12

Stromal derived factor–1

sHLA-G5

Soluble human leukocyte antigen G5

SL-1

Stromelysin-1

STC1

Stanniocalcin-1

S-TRAIL

Secretable form of TRAIL

TAF/CAF

Tumor-associated fibroblasts/carcinoma associated fibroblasts

TAM

Tumor-associated macrophages

TGF-β

Transforming growth factor-beta

Th1 cells

T Helper 1 cells

Th2 cells

T Helper 2 cells

TIMPs

Tissue inhibitor of metalloproteinases

TLS

Tertiary lymphoid structures

Tn-C

Tenascin-C

TNF

Tumor necrosis factor

TNF-α

Tumor necrosis factor-alpha

tPA

Tissue plasminogen activator

TRAIL

Tumor necrosis factor apoptosis inducing ligand

Tregs

T regulatory cells

Tsp-1

Thrombospondin-1

uPA

Urokinase plasminogen activator

uPAR

Urokinase plasminogen activator receptor

VEGF

Vascular endothelial growth factor

WAT

White adipose tissue

α-SMA

Alpha-smooth muscle actin

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Copyright information

© 2013 2012

Authors and Affiliations

  • Naomi D’souza
    • 1
  • Jorge Sans Burns
    • 1
  • Giulia Grisendi
    • 1
  • Olivia Candini
    • 1
  • Elena Veronesi
    • 1
  • Serena Piccinno
    • 1
  • Edwin M. Horwitz
    • 2
  • Paolo Paolucci
    • 1
  • Pierfranco Conte
    • 1
  • Massimo Dominici
    • 1
  1. 1.Department of Medical and Surgical Sciences for Children & AdultsUniversity Hospital of Modena and Reggio EmiliaModenaItaly
  2. 2.Division of OncologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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