The accumulation of mutations in genes responsible for regulating cell growth can cause normal cells to become malignant. The vast majority of cancer research to date has been conducted with a tumor-cell centric focus in mind, overlooking the potential role of tumor microenvironment in the growth and progression of this disease. Though tumors are well documented to control their own growth and progression through the expression of growth and regulatory factors, recent evidence has highlighted the crucial role that the malignant cell’s surroundings, in particular the tumor stroma, play in the initiation and progression of cancer.
The integrity and homeostasis of normal epithelial cells is dependent on their crosstalk with normal tissue stroma. However, when cells become malignant, alterations in the stroma occur, creating an environment, which encourages tumor invasion leading to metastasis. The tumor stroma is predominately comprised of fibroblasts, vasculature with endothelial cells and pericytes and structural proteins, which comprise the extracellular matrix (ECM). Tumors are interspersed with blood and lymph vessels plus bands of connective tissue that comprise the stroma’s physical structures. Cancer associated fibroblasts (CAFs), embedded in the connective tissue are the principle cell type within the tumor stroma of many cancers. Upon activation by tumor-secreted factors, CAFs release various growth factors, hormones, proteases and cytokines, which promote malignant growth, angiogenesis, tissue invasion and metastatic dissemination. Tumor cells are an important source of various chemoattractants that recruit immune cells to the tumor stromal environment, such as lymphocytes and macrophages. Tumor-associated macrophages (TAMs)have been shown to affect neoplastic cell growth, ECM remodeling, and furthermore some which express the Tie2 receptor on their cell surface contribute to neoangiogenesis.Furthermore, after recruiting TAMs to the tumor site, the tumor abolishes the macrophages’ ability to attack and destroy tumor cells.
Decades of cancer research focusing on the malignant cell itself combined with more recent observations revealing important roles for the tumor’s environment in the initiation and progression of cancer have vastly enhanced our understanding of cancer biology. Armed with an enhanced understanding of the pathways and cells underlying the pathogenesis and progression of this fatal disease is critical to the identification of new therapeutic targets, potentially including components of the tumor stroma.
Medical animation about the role of the stroma in cancer growth and development
Support for a growing tumor can be provided by its own stroma which consists of connective tissue and various cell types. The connective tissue provides a framework and physical support for the tumor, whereas the different cells contained within the stroma can release factors that promote the growth and development of the tumor. This medical animation provides information on the role of the stroma in tumor development and its potential as a therapeutic target.
This is an image of various tumor stromal elements including fibroblasts which are embedded within the connective tissue and secrete growth factors and components to build the extracellular matrix and lymphocytes and macrophageswhich are attracted by the release of chemoattractants by tumor.
This is an image of tumor associated macrophages. Macrophages can release several cytokines and growth factors that can promote the growth of cancers and tumors within the body.