Tumor Stroma Formation in Lung Cancer

Lung carcinomas are heterogeneous in composition. The malignant cells are surrounded by a specialized connective tissue called stroma, consisting of an extracellular matrix (ECM) and a cellular compartment made of fibroblasts, inflammatory cells and endothelial cells. The ability of carcinoma cells to induce a stroma is a phenotypic trait that is maintained at metastatic sites. Stromal tissue is qualitatively distinct from the connective tissue which develops in inflammatory conditions: for instance, stromal inflammatory and mesenchymal cells have distinct phenotypic characteristics, and specific spliced variants of ECM components, such as fibronectin and tenascin, have been reported in carcinomas. Blood vessels are another essential component of the stroma. A vascular supply is necessary for tumor growth over 2 mm3. This is achieved by the complex multistep process of angiogenesis (see chapter by Castronovo et al., this volume). Moreover, the stroma, as opposed to normal connective tissue, is an unstable structure, remodelled throughout tumor development. This plasticity, controlled in part by the neoplastic cells themselves, is the result of a spatially and temporally changing imbalance between the agonist and antagonist stromal mechanisms that control tumor progression.