Radiol Oncol 2002; 36(2): 168. 

Tumor progression and invasion 

Tamara T. Lah 

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology 
Večna pot 111, Ljubljana, Slovenija 


Cancer is the disease of the gene. The very first event that damages nuclear DNA is initiated by an initiator 
(substance, radiation), which may cause different effects, such as mutations, DNA breaks, etc, which may or 
may not cause cancer. Additional hits, which do lead to the development of cancer, are caused by tumor promoters. 
At present, detailed knowledge of all the events leading to a malignant disease, are not yet understood. 
Molecular description of tumor progression envisages that each type of cancer will progress in stages: the 
step-wise genetic changes accompanying this progression, are unique to each type of cancer. To study these 
events, various in vitro and in vivo approaches were developed. The first part of the workshop will be dedicated 
to the methodology used to identify DNA damage, while the second part will be dedicated to the experimental 
models used to identify biological markers, associated with tumor and/or endothelial cell invasion. 

Metastasis of primary tumors is comprised 
of biologically distinct steps and is rather inefficient 
process. Local tumor cell invasion is a 
common denominator in many of these steps 
and was first described by Liotta1 as a three-
step process, where, first specific attachment 

(I) is followed by the induction and/or release 
or hydrolytic – proteolytic – enzymes, which 
degrade (II) extracellular matrix components, 
thereby facilitating tumor cell locomotion (III) 
and penetratioan into the host tissues. Several 
experimental models are used to study the molecular 
mechanisms of invasion. Most in vitro 
invasion assays are using natural tissues, such 
as amnion membrane, eye lens and fragments 
of various tissues, such as chicken heart, mouse 
liver, lung, etc. Organotypic co-culture models 
were mostly used for studying brain tumor 
invasion. The most simple are invasion 
assays using modified Boyden chambers2,3 and 
Matrigel or other isolated proteins of extracellular 
matrix. However, the results may not be 
reproducible even when using the same system, 
due to several methodological problems, 
comprising variability in composition, concentration 
and preparation of Matrigel (or other 
proteins), quality of filters, treatment of cells 
(pH, trypsinization, organic solvents), chemoatractants, 
time of the assays and methods used 
for the quantitation of the invasion. The data in 
the literature confirmed that various proteinase 
inhibitors were effective in partial inhibition 
of invasion, indicating that one or several proteinases 
are involved in this process. The results 
on inhibition of invasion of breast tumour 
cells, using synthetic and natural (peptide) 
cysteine proteinase inhibitors are not yet conclusive, 
due to variability of methodological approaches, 
described in the literature. 

References 

1. 
Liota LA. Tumor invasion and metastasis. Role of 
extracellular matrix. Cancer Res 1989; 46: 1-7. 
2. 
Albini A, Iwamoto, Y, Kleinman HK, Martin GR, 
AAronson SA, Kozlowksi JM, McEwan RN. A rapid 
in vitro assay for quantiting the invasive potential 
of tumor cells. Cancer Res 1987; 47: 3239-45.