Cancer metastasis refers to the spread of cancer cells to
distant locations through the blood or lymphatic system.
Experimental evidence has shown that cancer cells are armed with
an array of proteolytic enzymes that appear to be essential for the
process of cancer dissemination.
Cancer metastasis is a complex phenomenon that involves
(1) proliferation of cancer cells, (2) survival of immune response,
(3) angiogenesis and nutritional supply to the cancer mass,
(4) local invasion and destruction,
(5) penetration of cancer cells through the blood or lymphatic vessel wall,
(6) embolization and clump formation of cancer cells in distant organs
and (7) growth of the metastatic cells.
The development of metastasis necessitates genetic changes of cancer cells
leading to the metastatic phenotype,
but the detailed mechanism is not fully understood yet.
Activation of a number of oncogenes has been associated with the
invasive, metastatic phenotype in different cancer types.
Rat mammary carcinoma cells transfected with the v-Ha-ras gene became
genetically unstable and tended to develop metastasis.
the detection of ErbB2 (gene) positive cells in the bone marrow
showed correlation with the incidence of metastasis.
Overexpression of c-myc, c-erb, c-Ki-ras, and hst oncogenes was
observed in metastatic gastric cancers.
Cancer can induce angiogenesis through release of a variety of factors.
Vascularization increases the probability of cancer metastasis.
The process of angiogenesis involves
(1) motility of endothelial cells toward the angiogenic stimulus,
(2) proteolysis for penetration
of the endothelial cell buds into the extracellular matrix, and
(3) proliferation of endothelial cells to form new capillaries.
It is important to know which genes are responsible for the expression
of the metastatic phenotype and understand how they are regulated.
Some genes actually play a role in suppressing metastasis.
The following genes are related to cancer metastasis:
The pGM21 gene: associated with high metastatic potential in rat
The nm23 gene: a metastasis suppressor gene with other possible functions
The maspin gene: a metastasis suppressor gene which is expressed
in normal mammary epithelial cells but not in most mammary
carcinoma cell lines
Treatment of Metastasis
Antimetastatic drugs are based on the ideas of inhibiting cancer cell
motility, penetration, attachment, or angiogenesis.
Drugs working on the genetic level are promising and currently
Ruddon, R.W. 1995. Cancer Biology. Oxford University Press, New York.