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


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


MSC Microenvironment Tumor stroma TAF TRAIL 





Adeno associated viruses


Antigen presenting cells


Angiopoietin 1


Basic fibroblast growth factor


Bone marrow




Cellular fibronectin


Cancer stem cells


Cytotoxic T Lymphocytes


Dendritic cells


Dickkopf-related protein-1


Death ligand


Extracellular matrix


Epidermal growth factor


Epithelial to mesenchymal transition


Endothelial to mesenchymal transition


Endothelial progenitor cells


Embryonic stem cell




Endothelin binding receptor


Focal adhesion kinase


Fibroblast activation protein


Formyl peptide receptor like-1


Fibroblast specific protein


Granulocyte-colony-stimulating factor


Granulocyte-macrophage-colony-stimulating factor


Human adipose-derived mesenchymal stromal/stem cells


Human bone marrow-derived mesenchymal stromal/stem cells


Hepatocarcinoma cancer


Hepatocyte growth factor


Human leukocyte antigen


Human leukocyte antigen and its ligand


Human mesenchymal stromal/stem cells


Heme oxygenase-1


Hematopoietic stem cells


Indolamin 2, 3-dioxygenase




Insulin growth factor




Leukemia inhibitory factor


Monocyte chemotactic protein-1


Macrophage-colony-stimulating factor


Myeloid derived suppressor cells




Matrix metalloproteinases


Mesenchymal stromal/stem cells


Nuclear factor-kappa B


non-Hodgkin lymphoma

NK cells

Natural killer cells


Nitric oxide


Non-small cell lung carcinoma


Osteogenesis imperfecta


Plasminogen activator inhibitor type-1


Plasminogen activator inhibitor type-2


Platelet derived growth factor


Plasma fibronectin


Prostaglandin E2


Platinum-induced polyunsaturated fatty acids


Placental growth factor


Reactive oxygen species


Severe combined immunodeficieny


Stromal derived factor–1


Soluble human leukocyte antigen G5






Secretable form of TRAIL


Tumor-associated fibroblasts/carcinoma associated fibroblasts


Tumor-associated macrophages


Transforming growth factor-beta

Th1 cells

T Helper 1 cells

Th2 cells

T Helper 2 cells


Tissue inhibitor of metalloproteinases


Tertiary lymphoid structures




Tumor necrosis factor


Tumor necrosis factor-alpha


Tissue plasminogen activator


Tumor necrosis factor apoptosis inducing ligand


T regulatory cells




Urokinase plasminogen activator


Urokinase plasminogen activator receptor


Vascular endothelial growth factor


White adipose tissue


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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