ARACHIDONIC ACID IN PULMONARY LARGE CELL CARCINOMA

花生四烯酸在肺大细胞癌中的作用

• 批准号: 4692203
• 负责人: S S LAU
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692203
• 关键词: arachidonate; carcinoma; cellular oncology; eicosanoid metabolism; fatty acid metabolism; host neoplasm interaction; human tissue; lung neoplasms; metastasis; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer pharmacology; neoplastic growth; prostaglandin E

Clinically, large cell carcinoma (LCC) is by far the least treatable lung cancer. Characterization of this subclass of carcinoma by an exclusive cell type is not possible even under electron microscopic examination. Thus, investigation of the biochemical and morphological features of human LCC is warranted. The pathobiology of human lung cancer is often associated with the biosynthesis and release of various biologically active substances by malignant cells. A number of studies have indicated that prostaglandins (PGs) and other eicosanoids may play a role in the pathobiology of malignant disease, i.e., tumor promotion, cellular proliferation and differentiation. One metabolite of arachidonic acid (AA), prostaglandin E2 (PGE2), has been implicated as a mediator of hypercalcemia associated with certain lung cancers. The leukotrienes participate in the initiation of immune and inflammatory responses and thus could play a role in host defense mechanisms in human lung cancer. Studies of the metabolism of AA were undertaken to determine the pathways of AA metabolism and the relevance of this metabolism in human LCC. Our preliminary studies demonstrated that a homogenous human LCC line, NCI-H460, unlike any other known human lung carcinoma cell line maintained in this laboratory possesses significantly higher PGE2 synthesis (6 fold) in the early passage (15) as compared to that in the late passage (93). Furthermore, the morphology of this cell line has changed. Originaly diagnosed as LCC (containing large amounts of endoplasmic reticulum), it was reclassified as a small cell carcinoma (exhibiting endocrine cell features) in passage 15 and it is now described as an oncocytoma (containing large numbers of mitochondria). The mechanism for such an alteration is unknown. To examine the role of AA metabolism in tumor development in vivo, cells from early and late passages of NCI-H460 will be injected into nude mice. The profile of AA metabolism in the primary tumor as well as in the metastases formation will be investigated.

在临床上，大细胞癌（LCC）是迄今为止最难治疗的肺