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Eric A. Mann, MD, PhD; Jeffrey D. Spiro, MD; Lei L. Chen, MD, PhD; Donald L. Kreutzer, PhD

Arch Otolaryngol Head Neck Surg. 1994;120(7):763-769.

Abstract
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 E₂ (PGE₂), leukotriene B₄ (LTB₄), 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 E₂, LTB₄, 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 PGE₂ (range, 324 to 2258 pg/g of tumor tissue) and LTB₄ (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 PGE₂ (range, 90 to 1160 pg/10⁶ cells), and half of the cultures produced LTB₄ (range, 100 to 1700 pg/10⁶ cells); none of the cultures or cell lines produced detectable levels of PAF. Interleukin 1 significantly enhanced production of PGE₂ 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 E₂, LTB₄, and PAF are present in the tumor microenvironment, where they may be involved in the local immunosuppression phenomenon seen in HNSCC. Both PGE₂ and LTB₄ 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 I and PGE₂ may interact in immunoregulation in the HNSCC tumor microenvironment.

(Arch Otolaryngol Head Neck Surg. 1994;120:763-769)

Author Affiliations
From the Division of Otolaryngology, Department of Surgery (Drs Mann and Spiro), Division of Hematology and Oncology, Department of Medicine (Dr Chen), and Department of Pathology (Dr Kreutzer), University of Connecticut Health Center, Farmington.

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