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Functional Hyaluronan Receptors Are Expressed on a Squamous Cell Lung Carcinoma Cell Line but not on Other Lung Carcinoma Cell Lines¹

Department of Medical and Physiological Chemistry, Uppsala University, Biomedical Center, Box 575, S-751 23 Uppsala [P. T., P. H.], and Departments of Lung Medicine [P. T.] and Oncology [J. B.], University Hospital, S-751 85 Uppsala, Sweden

We investigated the production of hyaluronan and the presence of hyaluronan receptors in a panel of human lung carcinoma cell lines, consisting of small cell carcinomas (SCLC) and non-small cell carcinomas (non-SCLC). These transformed cell lines produced only minute amounts of hyaluronan, whereas normal lung fibroblasts synthesized high amounts. CD44 molecules (an integral membrane glycoprotein suggested previously to function as a hyaluronan receptor) were differentially expressed on non-SCLC cell lines but essentially not on the SCLC cell lines. In contrast, RHAMM molecules (receptor for hyaluronan-mediated motility) were preferentially expressed on SCLC cells. Although all the lung tumor cell lines expressed various amounts of CD44 and RHAMM, only the SCLC line U-1752 could bind [³H]hyaluronan. The binding sites were saturated with about 19,700 hyaluronan molecules (M_r 1.4 x 10⁶) bound per cell with a K_d of 0.16 x 10^-9 M. CD44 molecules were responsible for the binding activity since Hermes-1 antibodies that block the binding of hyaluronan to CD44 blocked the binding of [³H]hyaluronan to U-1752 cells. 4-Phorbol 12-myristate 13-acetate (PMA) treatment of U-1752 cells both increased the hyaluronan-binding activity in U-1752 cells as well as induced abrogation of cell-cell and cell-matrix interactions. Addition of hyaluronan inhibited the PMA-induced disassembly of the cells. The fact that CD44 molecules are able to bind [³H]hyaluronan only on the SCLC line U-1752 but not on other lung carcinoma cell lines may be of value as a marker for squamous cell carcinoma differentiation. Furthermore, the inhibitory effect of hyaluronan on the PMA-promoted cell disassembly suggest that hyaluronan surrounding squamous cell carcinoma cells may affect their migration and invasiveness.

¹ This project was supported in part by grants from The Swedish Cancer Society, Gustaf V:s 80-årsfond, The Swedish Medical Research Council (O3X-4), Göran Gustafssons Stiftelse, and the Medical Faculty of Uppsala University.

² To whom requests for reprints should be addressed.

Received 4/ 4/95. Accepted 7/ 5/95.

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