PHOSPHOLIPID METABOLITE EXPRESSION BY HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Objective: To characterize the presence and production of various phospholipid metabolites by head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma cell lines in vitro and in vivo. Design: The HNSCC tumor homogenates and supernatants of HNSCC tumor cultures and established squamous cell carcinoma cell lines were assayed for prostaglandin E(2) (PGE(2)), leukotriene B-4 (LTB(4)), and platelet activating factor (PAF). In vitro experiments were carried out under baseline conditions or with exposure to several known immunomodulators (epidermal growth factor, bacterial lipopolysaccharide, and interleukin 1). Patients: The HNSCC tumor tissue was obtained from primary tumor or cervical lymph node metastasis of surgical resections. Main Outcome Measures: Prostaglandin E(2), LTB(4), and PAF were measured in tumor homogenates and cell culture supernatants using standardized radioimmunoassay kits. Results: All tumor homogenates (eight of eight) contained detectable levels of PGE, (range, 324 to 2258 pg/g of tumor tissue) and LTB(4) (range, 790 to 41 900 pg/g of tumor tissue); PAF was detected in six of eight homogenates (range, 7362 to 40 788 pg/g of tumor tissue). All of the short-term primary HNSCC tumor cultures and squamous carcinoma lines produced PGE(2) (range, 90 to 1160 pg/10(6) cells), and half of the cultures produced LTB(4) (range, 100 to 1700 pg/10(6) cells); none of the cultures or cell lines produced detectable levels of PAF. Interleukin 1 significantly enhanced production of PGE, by tumor cultures (P<.02). Characterization of tumor cultures with a fibroblast antibody marker, BR2, revealed that 26% to 64% of tumor culture cells were fibroblasts. Conclusions: Prostaglandin E(2), LTB(4), and PAF are present in the tumor microenvironment, where they may be involved in the local immunosuppression phenomenon seen in HNSCC. Both PGE(2) and LTB(4) were produced in vitro by tumor cultures and squamous cell carcinoma cell lines; PAF was not produced by tumor cultures in vitro and therefore may be a product of local immune cells in HNSCC in vivo. Interleukin 1 and PGE(2) may interact in immunoregulation in the HNSCC tumor microenvironment.