1. ^*Department of Pathology, Saga, Japan
2. ^†Division of Dermatology, Department of Internal Medicine, Saga Medical School, Saga, Japan

Correspondence: Dr Takuya Inoue, Department of Pathology, Saga Medical School, Nabeshima 5-1-1, Saga City, 849-8501, Japan. Email: g9701@post.saga-med.ac.jp

Received 22 May 2000; Revised 18 December 2000; Accepted 30 April 2001.

Abstract

Cancer cell–stromal cell interaction plays a crucial role in the malignant growth of cancer cells. In the skin, the main stromal cell types consist of dermal fibroblasts and subcutaneous adipocytes. Fibroblasts are shown to promote the invasive growth of various cancer cell types. The interaction between cancer cells and stromal adipocytes, however, has not been sufficiently studied even in cutaneous carcinoma. To address the effects of adipocytes on the biologic behavior of cancer cells, we examined the growth and differentiation of a squamous cell carcinoma cell line of the skin (DJM-1), using a three-dimensional collagen gel matrix culture with a cutaneous environmental factor, air exposure. The growth was estimated by the uptake of bromodeoxy-uridine (BrdU) for 24 h. The BrdU indices of DJM-1 cells in stromal-cell-free, fibroblast-containing, and adipocyte-containing conditions were 19.7 1.9%, 19.8 2.8%, and 4.7 1.4%, respectively, whereas the BrdU index on the gel containing both fibroblasts and adipocytes was 10.4 3.3%. In terms of differentiation, DJM-1 cells cocultured with adipocytes constructed the best-organized stratified layer with a cornified-like structure in all conditions above. The differentiation markers involucrin and cytokeratin 10 were immunohistochemically detected in this structure of DJM-1 cells. Adipocyte-induced phenomena were not affected distinctively by air exposure. These results indicate that adipocytes, but not fibroblasts, promote the differentiation of squamous cell carcinoma cells (DJM-1) and inhibit their growth. These adipocyte-induced phenomena were not completely inhibited by fibroblasts. In conclusion, we suggest that stromal adipocytes may be involved in the differentiating mechanisms of cutaneous carcinoma cells.