Mechanisms

For a tumour to invade and infiltrate locally, its cells must acquire the ability to proliferate and advance into the extracellular matrix. Basement membranes are one of the first barriers that need to be traversed and this may be achieved by tumour cells:

• binding to basement membrane laminin - provides a fixed point for cell movement
• secreting their own laminin - provides a link to type IV collagen in basement membranes
• binding adjacent fibronectin molecules

The dynamic interplay of interactions such as these ensures that the cell can fix onto a point in the direction that it is about to advance. However, a space must be created in which the cell can move: this is mainly achieved by degradation of the extracellular matrix. For example, human fibrosarcoma may utilise a type IV collagenase enzyme. A variety of other enzymes are also secreted, e.g. elastases and plasmin, to breakdown non-collagenous matrix. Cancer cells may also indirectly advance by stimulating host cells to secrete proteolytic enzymes.