Role of the host stroma in cancer and its therapeutic significance

Current cancer research focuses mainly upon the cancer cells in malignant tumours and is providing a growing database about aberrations in their genetic composition. However, tumours also contain non-cancerous host tissue, referred to as the stroma, which plays an active and indispensable role in tumour growth and influences the virulence of the neoplasm towards the host. Many cell types inhabit the stroma, amidst apparently inert fibrous and viscous matrix material, composed of complex polysaccharides, proteins and other molecules. Actually, all of these elements are in constant turnover, causing unpredictable evolution in the properties of the community. This article provides pathologic observations and data on reciprocal interactions between these stromal and neoplastic components of tumours and how they change during the course of the disease. Malignant progression depends upon dauntingly intricate communications between different specialised lineages within the cellular society, which enable rapid adaptation to changing circumstances. Opportunistic misuse of such communication networks enables tumour cells to recruit and incorporate adjacent normal stroma into their midst, so that they may grow, infiltrate and parasitise the host. The absolute dependency of primary tumours and metastases on their diverse stromal components for survival and their insatiable need to continuously recruit more stroma to support expansion, renders them vulnerable to strategies capable of disrupting the cellular interactions involved. This dependency is of critical importance for cancer therapy research, and proposed methods for turning this parasitic behaviour of tumours against themselves are suggested below.