Progression of weakly malignant clone cells derived from rat mammary carcinoma by host cells reactive to plastic plates.

Tumor progression is the process by which tumor cells acquire more malignant properties, such as invasiveness and metastasis, during tumor development. To elucidate mechanisms of tumor progression, we examined the role of interactions between the tumor and its host by using a cloned cell line, ER-1, which was derived from a rat mammary carcinoma. ER-1 is weakly tumorigenic and non-metastatic when s.c. injected into syngeneic hosts in single cell suspension. However, ER-1 cells show a high incidence of lethal growth when s.c. implanted (5 x 10(2) cells), being attached to a 10 x 5 x 1 mm polystyrene plate. Tumor cell lines (PLT) obtained from tumors which had arisen from the plate-attached ER-1 cells no longer required plates for their growth in normal hosts, and had acquired metastatic ability to the lungs. The malignant phenotypes of PLT were stable under a usual culture condition for at least 6 months. Furthermore, the incidence of tumor development increased when small numbers of ER-1 cells were injected onto plates (or at their periphery) which had previously been implanted s.c. without tumor cells. The tumorigenicity of ER-1 cells increased after they were cocultivated for more than 30 days with host reactive cells obtained from the tissues surrounding the plates. These results suggest that host cells reactive to the foreign body (plastic plate) may not only promote the local growth of ER-1 cells but also convert them into much more malignant tumors.

a rat mammary carcinoma

a weakly tumorigenic and non‐metastatic cell line derived from c‐SST‐2

a tumor cell line derived from the plate‐attached ER‐1 cells

6‐thioguanine

ouabain

ethyl methanesulfonate

Dulbecco's modified medium

newborn calf serum

phosphate‐buffered saline.