Anticancer Research, Vol. 7, pp. 1005-1010, 1987.
The paper synthesizes research on the in vitro interactions between human fibroblasts and malignant HeLa cells, challenging the common perception that normal tissue in a cancer patient simply capitulates to tumor growth. In the organism, normal physiological mechanisms prevent the anarchic growth seen in cancer. The author suggests that defense mechanisms against malignancy should be explored in healthy tissues or in patients with non-metastasizing tumors. The stroma, which grows in tandem with neoplastic cells, displays significant variability across different tumors, highlighting its importance in tumor progression. Furthermore, stromal development may represent an immune reaction that impedes tumor invasion, as seen in the fibrous tissue left behind by completely regressed tumors.
By replacing tumor stromal cells with normal fibroblasts in a controlled in vitro model, researchers can observe how normal tissue first reacts to neoplastic cells. Previous experiments have demonstrated that HeLa cells and fibroblasts act as mutual chemoattractants. Moving fibroblasts preferentially direct themselves toward HeLa cells, showing a clear tendency to encircle them. When fibroblasts and HeLa cells are cocultured, they communicate by exchanging molecules, such as H-UdR. Furthermore, if fibroblasts are added to a nearly confluent monolayer of HeLa cells, they attach to the available space without being overlapped by the cancer cells.
The key finding discussed is the ability of fibroblasts to destroy HeLa cells under specific conditions. This cytocidal effect requires a low initial cell inoculum to allow for prolonged observation (15-20 days), a high fibroblast-to-HeLa ratio (10:1) to prevent the faster-growing HeLa cells from overgrowing, and vital medium replacement every two days. When these parameters are carefully monitored, the fibroblasts flourish and eventually form a dense surrounding bow (DSB) around the HeLa colonies. If the medium is not renewed, HeLa cells can invade this fibroblast barrier; however, with regular feeding, the fibroblasts actively attack and destroy the HeLa cells, leading to extensive nuclear and cytoplasmic fragmentation. These findings suggest that stromal fibroblasts possess a latent capacity to actively defend against cancer cells.
