The role of the stroma in carcinogenesis

Abstract

This systematic review considers the most recent attitudes and news regarding the influence of the stroma on tumor initiation and progression. It is now widely accepted that tumor stroma plays an active role in carcinogenesis. Many different signaling molecules, ligands and signaling pathways recently have been discovered. This review considers the complexity of interactions between malignant cells and its stroma (cross-talk). The recent advances and better understanding of the tumor-stroma interactions will have important impact on the new and combined therapeutic approaches and modalities.

FIGURE 1

The role of TGF-β in carcinogenesis. In normal cells TGF-β acts via signaling pathways which cause cell cycle arrest in Gl phase, thus inhibiting proliferation and stimulating differentiation or apoptosis. During carcinogenesis, the mutations of the genes involved in TGF-β signaling pathways occur. This makes tumor cells resistant on TGF-β activities. It results in increased tumor proliferation and production of TGF-β by stromal fibroblasts. Then TGF-β acts on stromal cells including immunocytes, endothelial cells and smooth muscle cells showing its immunosuppressive and proangiogenic activities. All these activities lead to increased tumor aggressiveness (11).

FIGURE 2

Molecular mediators of epithelium-stroma interactions. The cells within tumor tissue communicate during carcinogenesis via growth factors, chemokines and cytokines. A: Different paracrine signals; B: TGF-β is specific mediator since it can show dual effects (inhibitory and stimulating) (8)