Influence of a lymph node environment on invasiveness of metastatic tumor cells.

BACKGROUND

We investigated the possibility that lymph nodes might increase metastatic efficiency of tumor cells lodged there by measuring changes in tumor cell invasiveness after physical contact with an in vitro approximation of a lymph node environment.

STUDY DESIGN

The experimental model involved growing Lewis lung carcinoma (LL) or B16 melanoma cells on microcarrier beads, rolling them on a "lymph node endothelial surface," which was created by growing endothelial cells on a differentiating acid extract of lymph node biomatrix, and testing the ability of those tumor cells to invade across matrigel-coated filters at rest (buffer) and in response to a chemotactic stimulus (3T3 conditioned media).

RESULTS

Compared with contact with plastic, LL invasiveness was increased fivefold (buffer or conditioned media) and B16 invasiveness fourfold (conditioned media). Tumor cell invasiveness was not increased by exposure to the acid extract of biomatrix alone. Invasiveness to buffer or conditioned media after exposure to endothelial cells alone was 70 and 54 percent (LL) and 42 and 80 percent (B16), respectively, of the invasiveness induced by exposure to both. Compared with invasiveness induced by exposure to lymph node (100 percent), exposure to a "lung endothelial surface" induced invasiveness of 63 and 85 percent (LL) and 40 and 52 percent (B16) to buffer and conditioned media, respectively. Exposure to a hepatic endothelial surface induced invasiveness similar to that induced by lymph node; 90 and 82 percent (LL) and 110 and 86 percent (B16) of lymph node-induced invasiveness.

CONCLUSIONS

A lymph node environment may modulate the metastatic potential of tumor cells.