Invasiveness of renal cell carcinoma--an in vitro model

The invasive properties of human renal cell carcinoma were tested on a gel-like reconstituted basement membrane matrix extracted from Engelbreth-Holm-Swarm transplantable mouse tumor (Matrigel). Both high-grade (Fuhrmans's nuclear grade III) and low-grade (Fuhrman's nuclear grade I) renal carcinoma cells as well as normal human renal tubular cells were seeded onto a thin-layered, full-strength gel (1-2 mm). The normal tubular cells migrated to form small irregular colonies interconnected by polygonal networks of cell cords and grew along the surface contour of the gel. No evidence of distortion, dissolution, or invasion of underlying gel was observed but a thin layer of electron dense lamina was found to form underneath the cells. The noninvasive morphology was observed to have lasted for more than 3 weeks. On the contrary, both low-grade and high-grade carcinoma cells formed individual colonies and invaded the underlying matrix by developing invasion buds and subsequently cords or tubule-like structures of variable length. No basement-membrane-like electron dense deposit was observed at the cell-matrix interface. The observation that the mean invasion depth was higher in high nuclear grade carcinoma has significant implications on the association between invasiveness and nuclear grade. The findings that cancer cells closely contacted the surrounding matrix and reorganized the matrix in the immediate vicinity provided additional evidence of cell-matrix interaction.