IDENTIFICATION OF TYPE-I COLLAGEN-PRODUCING CELLS IN HUMAN GASTROINTESTINAL CARCINOMAS BY NONRADIOACTIVE INSITU HYBRIDIZATION AND IMMUNOELECTRON MICROSCOPY

Invasive growth of cancer cells induces desmoplastic reaction as one of the host reactions. It has been a matter of controversy whether stromal collagen is produced by cancer cells or stromal fibroblasts. In the present study, we investigated the cellular origin of Type I collagen in human gastrointestinal carcinomas by in situ hybridization and immunoelectron microscopy. In situ hybridization technique with digoxigenin-labeled RNA probes revealed that spindle-shaped fibroblasts in the stromal area were abundantly positive for transcripts of pro alpha-1(I) collagen in intestinal-type adenocarcinoma. Gland-forming carcinoma cells were negative. In diffuse-type carcinoma of the stomach, spindle-shaped or stellate fibroblasts were positive, whereas dissociated, oval carcinoma cells were negative. A precise determination of cell type was done by immunoelectron microscopy. Intracellular immunoreactivity for Type I collagen was observed in rough endoplasmic reticulum of fibroblasts (including myofibroblasts) in the stromal area. No definite reactivity was obtained in cancer cells by either in situ hybridization or immunoelectron microscopy. Our results indicated that stromal Type I collagen is produced by stromal fibroblasts, which are activated by cancer invasion.