Biology of metastasis

✍ Scribed by P. Frost; I. J. Fidler

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 405 KB
• Volume: 58
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19860715)58:2+<550::aid-cncr2820581324>3.0.co;2-z

✦ Synopsis

The acquisition by tumor cells of the ability to metastasize is the critical event in the clinical course of most human neoplastic disease. While metastasis plays a pivotal role in the ultimate success or failure of therapy, it is in fact a result of a more insidious malignant process termed tumor progression. It is the progression of tumors from a less to a more malignant phenotype that results in tumor heterogeneity and the selection of cells with a more malignant (metastatic) phenotype. The development of metastases is thus integrally related to the mechanisms of tumor progression, which in turn is likely due to the instability of the tumor cell genome. The authors' thesis is that metastatic tumor cells are a selected population derived from a heterogenous parent tumor which contains many clones with different phenotypes. This discussion will, therefore, address the role of tumor genomic instability as a hasis for the selection of metastatic cells.

Cancer 58550-553, 1986.

HE DEVELOPMENT O F METASTASES represents the le-

T thal event in the clinical course of most neoplastic diseases. While primary tumors can be surgically resected or irradiated, it is usually difficult to use these therapeutic modalities against disseminated cancer without severely damaging normal tissues. Metastasis thus represents a critical challenge to the therapy of cancer, and because of its lethality, a major focus for basic cancer research over the past decades.

How do metastatic tumor cells develop? In addressing this issue, one must first take note of the fact that metastatic tumor cells cannot perform physiologic functions for which there is not a normal counterpart cell. Lymphocytes, monocytes, and polymorphonuclear neutrophils are all capable of invading tissues in large numbers and accumulating at inflammatory sites. What is unusual about tumor cells, particularly epithelial tumor cells, is that mature adult epithelial cells do not normally migrate through the blood stream and/or lymphatics and ultimately invade unrelated organs. However, epithelial cells do migrate during embryogenesis and, more importantly, contain all the genetic information necessary for such functions, although these genes are not normally expressed. This implies that the potential ability for a cell