Molecular mechanism of tumor progression. From Krompecher to the DNA microarray

Rate limiting steps of the metastatic cascade are proliferation-independent cellular events integrated into the common sequence of tumor cell-extracellular matrix interactions (adhesion, degradation, migration). The two common dissemination forms, lymphatic and hematogenous, are highly similar in respect of the individual steps, but fundamentally different in respect of tissue specificity. Although the scheme of the metastatic cascade is well known for some time, its tumor type-specific molecular characteristics are poorly understood. This is based on the diversity in the matrix receptors and their alterations during tumor progression, in the mechanism of locomotion of various cancer cell types, and on the diversity and cancer specific alterations in the tyrosine kinome. Application of the techniques of global gene expression- and proteome-analyses for the comparative studies of non-metastatic, locally invasive and metastatic cancer types suggests that we can identify reliable progression markers and specific targets of tumor dissemination.