Mann E A, Spiro J D, Chen L L, Kreutzer D L
Department of Surgery, University of Connecticut Health Center, Farmington.
Arch Otolaryngol Head Neck Surg. 1994 Jul;120(7):763-9. doi: 10.1001/archotol.1994.01880310065012.
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.
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).
The HNSCC tumor tissue was obtained from primary tumor or cervical lymph node metastasis of surgical resections.
Prostaglandin E2, LTB4, and PAF were measured in tumor homogenates and cell culture supernatants using standardized radioimmunoassay kits.
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/10(6) cells), and half of the cultures produced LTB4 (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 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.
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 1 and PGE2 may interact in immunoregulation in the HNSCC tumor microenvironment.
在体外和体内表征头颈部鳞状细胞癌（HNSCC）及鳞状细胞癌细胞系中各种磷脂代谢产物的存在及产生情况。
对头颈部鳞状细胞癌肿瘤匀浆、头颈部鳞状细胞癌肿瘤培养物上清液以及已建立的鳞状细胞癌细胞系进行前列腺素E2（PGE2）、白三烯B4（LTB4）和血小板活化因子（PAF）检测。体外实验在基线条件下或暴露于几种已知免疫调节剂（表皮生长因子、细菌脂多糖和白细胞介素1）的情况下进行。
头颈部鳞状细胞癌肿瘤组织取自手术切除的原发性肿瘤或颈部淋巴结转移灶。
使用标准化放射免疫分析试剂盒检测肿瘤匀浆和细胞培养上清液中的前列腺素E2、白三烯B4和血小板活化因子。
所有肿瘤匀浆（8份样本中的8份）均含有可检测水平的前列腺素E2（范围为324至2258 pg/g肿瘤组织）和白三烯B4（范围为790至41,900 pg/g肿瘤组织）；8份匀浆中有6份检测到血小板活化因子（范围为7362至40,788 pg/g肿瘤组织）。所有短期原发性头颈部鳞状细胞癌肿瘤培养物和鳞状癌细胞系均产生前列腺素E2（范围为每10⁶个细胞90至1160 pg），半数培养物产生白三烯B4（范围为每10⁶个细胞100至1700 pg）；所有培养物或细胞系均未产生可检测水平的血小板活化因子。白细胞介素1显著增强肿瘤培养物中前列腺素E2的产生（P < 0.02）。用成纤维细胞抗体标志物BR2对肿瘤培养物进行表征，结果显示26%至64%的肿瘤培养细胞为成纤维细胞。
前列腺素E2、白三烯B4和血小板活化因子存在于肿瘤微环境中，它们可能参与了头颈部鳞状细胞癌中所见的局部免疫抑制现象。肿瘤培养物和鳞状细胞癌细胞系在体外均产生前列腺素E2和白三烯B4；血小板活化因子在体外肿瘤培养物中未产生，因此可能是头颈部鳞状细胞癌体内局部免疫细胞的产物。白细胞介素1和前列腺素E2可能在头颈部鳞状细胞癌肿瘤微环境的免疫调节中相互作用。
