Regulatory pathways in tumor growth and invasion.

Human tumor cells constitutively produce a variety of growth factors, cytokines, chemoattractants, motility factors, and proteolytic enzymes and their inhibitors. Juxtaposed normal cells such as fibroblasts, endothelial cells, and monocytes are also potential producers of most of these factors but, in general, they require specific signals to trigger synthesis and/or to release biologically active factors. Growth stimulation of normal and malignant cells, angiogenesis, and stroma formation within malignant lesions, tissue degradation by invasive tumor cells, cell motility, detachment of tumor cells from lesions and/or attachment to basement membranes involve complex interactions between autocrine, paracrine, and endocrine factors. Despite the complexity of such interactions, preliminary regulatory pathways can now be proposed that may help to explain the role for both positive and negative regulators in tumor development, growth, and invasion.