Why do cancer cells in an organ make the organ less efficient?
Answers
Explanation:
Different organs act together through blood and lymphatic vessels to form the organism. ... They contain multiple cell types and extracellular matrix components and develop through complex interactions between these different components of the tissues using processes that often resemble those used by developing organs
Abstract
Solid tumors are not simply clones of cancer cells. Instead, they are abnormal organs composed of multiple cell types and extracellular matrix. Some aspects of tumor development resemble processes seen in developing organs, while others are more akin to tissue remodeling. Some microenvironments, particularly those associated with tissue injury, are favorable for progression of mutant cells while others restrict it. Cancer cells can also instruct surrounding tissues to undergo changes that promote malignancy. Understanding the complex ways in which cancer cells interact with their surroundings, both locally in the tumor organ and systemically in the body as a whole, has implications for effective cancer prevention and therapy.
INTRODUCTION
Cells and extracellular matrix (ECM) form tissues, and collections of tissues join together in structural and functional units to form organs. Different organs act together through blood and lymphatic vessels to form the organism. Solid tumors are not random mixtures of cells and ECM, but rather resemble organs, although structurally and functionally abnormal. They contain multiple cell types and extracellular matrix components and develop through complex interactions between these different components of the tissues using processes that often resemble those used by developing organs. Tumors interact with the rest of the organism, similarly to normal organs. However, whereas normal organs have functions that support the survival of the organism, the systemic effects of the tumor organ often are what ultimately kill the patient. Thinking of tumors as organs may allow us to better understand the processes that govern how solid tumors develop and progress.
STROMAL COMPONENTS OF THE TUMOR ORGAN
Organs are composed of the cells that perform the main organ function (e.g., secrete hormones or enzymes) and the stroma (from Latin or Greek, often translated as “mat” or “bed”), the supportive framework of an organ. The stroma can be divided into several classes: the ECM, which is composed of proteoglycans, hyaluronic acid and fibrous proteins (e.g., collagen, fibronectin and laminin), and stromal cells. The stromal cells include mesenchymal supporting cells (e.g., fibroblasts and adipocytes), cells of the vascular system, and cells of the immune system. Various peptide factors (e.g., growth factors, chemokines, cytokines, antibodies) and metabolites are also found in the stroma. The stroma is essential for normal organ development (e.g., Cunha, 2008; Puri and Hebrok, 2010; Wiseman and Werb, 2002). Different components of the tumor stroma similarly influence the progression of the tumor (Table 1). As tumors develop and progress, they undergo dramatic morphological changes (Figure 1A; Egeblad et al., 2008; Lin et al., 2003), which also involves the stroma (Figure 1B, C & D; Egeblad et al., 2008; Levental et al., 2009; Lin et al., 2006; Provenzano et al., 2006). The importance of stage-specific changes of the stroma is not yet completely clear. However, in most cases the stroma of the later stages is more supportive of tumor progression than the stroma of early stages. Examples of stromal components that have been proposed to have a more pronounced tumor-promoting function in advanced stages than in earlier stages are fibroblasts, type I collagen and the immune cell infiltrate, as described below.
Carcinoma-associated fibroblasts
Fibroblasts are mesenchymally derived cells present in the stroma of most tissues. DurinCAFs (FWeinberand β angi