Tumor cell invasion and gap junctional communication. II. Normal and malignant cells confronted in multicell...

The invasive behavior of five tumor cell lines was investigated with an in vitro invasion assay developed by Mareel et al. Spheroids of all 5 cell lines readily attached to precultured heart fragments (PHF), resulting in confronting pairs. Tumor cells (BICR/M1Rk, C6, and EMT6/Ro) which communicated with the host tissue via gap junctions, rapidly invaded the PHF within 3 days. Population doubling time or migratory activities had no influence on the invasion process. The noncoupled HeLa and L cells formed a cellular capsule around the PHF and showed no invasive activities. HeLa cells, however, started to destroy the PHF after 4 days. We suggest a mechanism different from that of coupled tumor cells. Epithelioid HeLa cells are linked by numerous tight junctions and may, therefore, cut off the nutrition supply for the inner-laying PHF, resulting in a disintegration of the heart tissue.