Am J Cancer Res 2011;1(6):787-805

Review Article
Understanding tumor-stroma interplays for targeted therapies by armed
mesenchymal stromal progenitors: the mesenkillers

Giulia Grisendi, Rita Bussolari, Elena Veronesi, Serena Piccinno, Jorge Burns, Giorgio De Santis, Pietro Loschi, Marco Pignatti,
Fabrizio Di Benedetto, Roberto Ballarin, Carmela Di Gregorio, Valentina Guarneri, Lino Piccinini, Edwin M. Horwitz, Paolo
Paolucci, PierFranco Conte, Massimo Dominici

Division of Oncology, Department of Oncology, Hematology and Respiratory Diseases, University-Hospital of Modena and
Reggio Emilia, Modena, Italy; Unit of Paediatric Oncology, Haematology and Marrow Transplantation, Department of Mother and
Child, Modena; Unit of Plastic Surgery, Department of Head & Neck Surgery, Modena; Unit of Hepato-Pancreato-Biliary and
Transplant Surgery, Department of General Surgery, Modena; Section of Pathology, Department of Pathologic Anatomy and
Forensic Medicine, Modena; Division of Oncology/Blood and Marrow Transplantation, The Children’s Hospital of Philadelphia
and The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Received April 24, 2011; accepted May 17, 2011; Epub May 28, 2011; Published June 30, 2011

Abstract: Tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surrounding
cells constituting the tumor stroma (TS).  In recent years, the importance of TS for cancer initiation, development, local invasion
and metastases became increasingly clear allowing the identification of TS as one of the possible ways to indirectly target
tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts (TAF) play a crucial role providing both
functional and supportive environments. During both tumor and stroma development, several findings suggest that TAF could be
recruited from different sources such as locally derived host fibroblasts, via epithelial/endothelial mesenchymal transitions or
form circulating pools of fibroblasts deriving form mesenchymal progenitors, namely mesenchymal stem/stromal cells (MSC).
These insights prompted scientists to identify multimodal approaches to target TS by biomolecules, monoclonal antibodies and,
more recently, via cell based strategies. These latter appear extremely promising, although associated with still debated and
unclear findings. This review discusses on crosstalk between cancers and their stroma, dissecting specific tumor types, such
as sarcoma, pancreatic and breast carcinoma where stroma plays distinct paradigmatic roles. The recognition of these distinct
stromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TS by novel
compounds and/or MSC having specific killing activities. (AJCR0000064).

Keywords: Tumor Stroma, TAF, mesenchymal stem/stromal cells, TRAIL

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Address all correspondence to:
Massimo Dominici, MD
Department of Oncology, Hematology and Respiratory Diseases
University-Hospital of Modena and Reggio Emilia
Via del Pozzo, 71; 41100, Modena, Italy
Tel: 0039-059-422-2858
Fax: 0039-059-422-3341
E-mail:
massimo.dominici@unimore.it
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American Journal of Cancer Research
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