title: Tumor-stroma crosstalk: targeting stroma in breast cancer.
abstract: OBJECTIVE
  Combinatorial strategies in cancer medicine will not only target cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. The aim of the present review is to define the roles of the tumor microenvironment in primary and metastatic breast cancer progression.
  
  
  RESULTS
  The cancer microenvironment is composed of nontransformed host stromal cells, such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The stromal constituents contribute to the core and emergent hallmarks of cancer. In particular, they can boost sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction.
  
  
  CONCLUSIONS
  The stromal cells play a role in enabling or enhancing multiple hallmark capabilities in tumor microenvironment. This is a background for therapeutic-targeting strategies aimed to abrogate the stroma's contribution. Targeting tumor-associated fibroblasts, macrophages, angiogenesis and enhancing immune response may represent a paradigm-shifting approach to treating human cancer in the near future.
authors.affiliation: Division of Experimental Therapeutics, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Criscitiello
authors.forename: Angela
authors.initials: A
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D020239:Receptor Cross-Talk / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology*