Tumor cell interactions with the extracellular matrix during invasion and metastasis

WG Stetler-Stevenson, S Aznavoorian… - Annual review of cell …, 1993 - annualreviews.org
WG Stetler-Stevenson, S Aznavoorian, LA Liotta
Annual review of cell biology, 1993annualreviews.org
Malignancy is defined as neoplastic growth that tends to metastasize. Thus by definition
metastatic ability is the correlate of malignant potential. The fonnation of metastatic foci is the
most life-threatening aspect of malignant neoplasia. Occult metastatic tumor cells may
persist in a donnant state for years after the resection or elimination of the primary tumor
(Meltzer 1990; Zajicek 1987). They can then be activated by as yet unidentified stimuli and
metastatic foci suddenly develop in an explosive fashion, which results in a rapid demise of …
Malignancy is defined as neoplastic growth that tends to metastasize. Thus by definition metastatic ability is the correlate of malignant potential. The fonnation of metastatic foci is the most life-threatening aspect of malignant neoplasia. Occult metastatic tumor cells may persist in a donnant state for years after the resection or elimination of the primary tumor (Meltzer 1990; Zajicek 1987). They can then be activated by as yet unidentified stimuli and metastatic foci suddenly develop in an explosive fashion, which results in a rapid demise of the cancer patient. Most cancer deaths are due to the metastatic disease that remains resistant to conventional therapies. The primary aim of research into the mechanisms of tumor invasion and metas tasis fonnation is to identify new strategies for more effective therapy against this most deadly aspect of human cancer. The study of the genetic alterations associated with human tumor pro gression has yielded great insight into the mechanisms of oncogenesis (Bishop 1991; Fearon & Vogel stein 1990; Fidler & Radinsky 1990). Studies have clearly shown that the tumor development (tumorigenicity) and sub sequent metastatic behavior (malignant potential) are under separate genetic control (Garbisa et a1 1987; Muschel et al 1985). Genetic studies have demonstrated that establishment of a primary tumor focus is the result of multiple genetic alterations leading to uncontrolled tumor cell growth. These alterations include the loss or inactivation of anti-oncogenes as well as the activation of cellular proto-oncogenes. The genetic alterations associated with oncogenic transformation may occur in a random order and the resulting tumorigenicity is the net sum of these genetic changes. To date a single gene has not been identified that regulates the entire metastatic process. However, this is not surprising if we consider the multistep nature of metastasis fonnation, and that the genetic approach requires isolation and independent characterization of the multiple genetic alterations that may occur at each step.
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