Tumor Invasion and Metastases
A metastatic colony is the end result of a complicated series of tumor—host interactions.1,2 Potential mechanisms underlying this complex process are outlined in Table I. In this regard, primary tumor initiation and promotion are followed by the transition from in situ to locally invasive cancer and angiogenesis.3–6 Newly formed tumor vessels are often defective and easily invaded by tumor cells within the primary mass. At the invasion front, tumor cells also invade pre-established host blood vessels. Tumor cells are discharged into the venous drainage in single cell form and in clumps. For rapidly growing tumors 1 cm in size, millions of tumor cells can be shed into the circulation every day. Fortunately for the patient, only a very small percentage (< .01%) of circulating tumor cells initiate metastatic colonies. Tumors generally lack a well-formed lymphatic network. Therefore, communication of tumor cells with lymphatic channels occurs only at the tumor periphery and not within the tumor mass. Tumor cells entering the lymphatic drainage are carried to regional lymph nodes where they arrest in the subcapsular sinus. Within 10–60 min after initial arrest in the lymph node, a significant fraction of the tumor cells detach and enter the efferent lymphatics. These tumor cells eventually end up in the regional or systemic venous drainage due to the existence of numerous lymphatic—hematogenous communications. Thus, the regional lymph node does not function as a true mechanical barrier to tumor dissemination. Lymphatic and hematogenous dissemination occurs in parallel (see also Chapter 28).
KeywordsBasement Membrane Circulate Tumor Cell Pertussis Toxin Human Melanoma Cell Metastatic Phenotype
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