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. Author manuscript; available in PMC: 2011 Jun 15.
Published in final edited form as: Dev Cell. 2010 Jun 15;18(6):884–901. doi: 10.1016/j.devcel.2010.05.012

Figure 2. Interactions between cancer cells and stromal components influence tumor growth and progression.

Figure 2

(A) Interactions with mesenchymal cells. In hyperplastic tissues, normal epithelium and fibroblasts may exert a tumor-inhibiting effect. As cancer cells begin to expand, they also produce factors that activate myofibroblasts and recruit carcinoma-associated fibroblasts. These mesenchymal cell types, as well as adipocytes, are responsible for many of the tumor-associated changes in extracellular matrix (ECM).

(B) Recruitment of cells of the innate and adaptive immune compartment to a carcinoma. The immune cells are found both in the stroma at the invading edge of the carcinoma and infiltrating the tumor. Inflammatory cells, including neutrophils and macrophages, are frequently the first immune cells recruited to the tumor, and may be either tumor-promoting or tumor-inhibiting depending on their polarization. Another inflammatory cell type, the mast cell, is also recruited early and promotes tumor progression by releasing proteases that activate angiogenesis. Dendritic cells are primarily tumor-inhibiting as they support immunosurveillance and release signals that activate cytotoxic T cells. In contrast, myeloid-derived suppressor cells function to inhibit T cell activation. Natural killer cells and different types of T cells may have either pro- or anti-tumor functions, depending on their mode of activation. Immunoglobulins released by B cells promote tumor growth by initiation of the inflammatory response.

(C) Formation of metastases. At sites of vascular leakage, fibronectin is deposited and vascular endothelial growth factor receptor 1 (VEGFR1)-positive bone marrow-derived cells exit the circulation where they promote the establishment of the future metastases. They are involved in angiogenesis at the metastatic site through secretion of VEGF and degradation of the ECM by the release of MMP9. Circulating cancer cells reach the pre-metastatic site, sometimes covered by activated platelets, which protect them while they are in blood vessels and facilitate adhesion to the endothelial wall at the secondary site.