Mechanisms of tumor invasion: evidence from in vivo observations.

The major mechanisms of tumor invasion in vivo are discussed in the present review. A special emphasis is placed on tumor dedifferentiation which has proved to be of paramount importance for the invasion process. Based on in vivo observations obtained from various human and animal tumors a concept for the mechanism of tumor invasion is proposed which mainly comprises the following basic events: the first and essential step in tumor invasion is the tumor dedifferentiation and dissociation at the invasion front. This apparently temporary and reversible process mobilizes the tumor cells out of the main tumor bulk and enables them to invade the host tissue by active locomotion. This mechanism is essentially supported by an interstitial edema in the host tissue adjacent to the tumor periphery, which causes an 'opening and widening' of the host intercellular spaces. Enzymatic changes in the micromilieu of the extracellular matrix may contribute to this process. The tumor cell proliferation completes the invasion process in so far, as the invading tumor cells are still able to proliferate, leading this way to expanding tumor cell nests in the host tissue which have the potency to redifferentiate. The expansive growth of these tumor cell nests results in a progressive atrophy of the host tissue, mainly caused by an increasing compression and a competitive withdrawal of oxygen and other nutrients by the tumor cells. The overall picture of tumor invasion can therefore be considered as a repetitive cycle of active tumor cell locomotion followed by focal tumor cell proliferation in the host tissue.