dinoprost and Carcinoma--Squamous-Cell

We studied the response of a human squamous cell carcinoma cell line, SCC-12F, to human complement attack and found that the cells were completely resistant to complement lysis. In the absence of lysis, there was significant C3 deposition and C5b-9 deposition on the cells. Removal of the lipid-linked complement regulatory proteins CD59 and decay-accelerating factor (DAF) by treatment of the cells with phosphatidylinositol-specific phospholipase C (PIPLC) resulted in increased C3b and C5b-9 deposition on the cells and a slight increase in cell death. Treatment of the cells with complement caused them to release membrane vesicles containing the terminal complement proteins. In addition, complement induced SCC-12F to produce significant amounts of prostaglandin F2alpha (PGF2alpha). We conclude that CD59 and DAF are important in the resistance of SCC-12F to complement and that these cells produce membrane vesicles and PGF2alpha in response to complement attack. These responses, in the absence of cell death, may be important in the pathogenesis of inflammatory skin disease in which complement is deposited.

Topics: Animals; Carcinoma, Squamous Cell; Complement Inactivator Proteins; Complement Membrane Attack Complex; Complement System Proteins; Cytotoxicity, Immunologic; Dinoprost; Facial Neoplasms; Humans; Immune Sera; Keratinocytes; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoinositide Phospholipase C; Rabbits; Skin Neoplasms; Tumor Cells, Cultured; Type C Phospholipases

Prostaglandins may inhibit or promote tumor cell replication, depending on the cell system that is investigated. In our laboratory, we have established and characterized four different specific human cancer cell lines. The objectives of this study were to examine and compare the prostaglandin endoperoxide synthase (PG synthase, EC 1.14.99.1) activity of these cell lines by measuring the conversion of arachidonate to 3H-PGE2 and 3H-PGF2 alpha. We found that the oral epidermal carcinoma cell line (OEC-M1) had a moderate degree of PG synthase activity. Enzyme activity could be partially blocked (statistically significant) by the addition of epidermal growth factor (EGF) at 20 ng/mL and almost completely inhibited by platelet-derived growth factor at (PDGF) 20 mU/mL. By contrast, we discovered that the human breast adenocarcinoma cell line (BC-M1) did not contain significant PG synthase, and enzyme activity could be significantly activated by the addition of epidermal growth factor at 20 ng/mL and platelet-derived growth factor at 20 mU/mL. We also found that the human stomach adenocarcinoma cell line (SCM-1) had a significant amount of PG synthase activity, and these PG synthase activities were not activated or inhibited by EGF at 20 ng/mL or PDGF at 20 mU/mL. Furthermore, the human fibrosarcoma (FS-M1) cell line also contained a moderate degree of PG synthase activity, which could be significantly inhibited by PDGF at 20 mU/mL but was not inhibited by EGF at 20 ng/mL. The results suggest that EGF and PDGF may be involved in the regulation of the PG synthase activities of human oral, breast, stomach, and fibrosarcoma cancer cells.

Topics: Adenocarcinoma; Breast Neoplasms; Buttocks; Carcinoma, Squamous Cell; Chromatography, Thin Layer; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Enzyme Activation; Epidermal Growth Factor; Female; Fibrosarcoma; Gingival Neoplasms; Humans; Organ Specificity; Platelet-Derived Growth Factor; Prostaglandin-Endoperoxide Synthases; Stomach Neoplasms; Tumor Cells, Cultured

The levels of prostaglandins E, E2 and F2a (PGE, PGE2, PGF2a) in plasma of NPC patients, patients with other tumors and normal individuals were monitored by radioimmunoassay. The results showed that PGE and PGE2 levels in the plasma of NPC and other cancer patients were significantly higher but the PGF2a/PGE2 ratio was obviously lower than that of the normal (P less than 0.05). But there were not much changes in the PGF2a levels (P greater than 0.05). However, no difference was found between the PG8 levels of the NPC and the other cancer patients (P greater than 0.05). Neither were there any significant changes in the PGE2 and PGF2a plasma levels and ratio of PGF2a/PGE2 in 26 NPC patients staged according to TNM classification. It is indicated that there is a relation between PGE, PGE2 and nasopharyngeal carcinoma.

Topics: Adult; Carcinoma, Squamous Cell; Cyclohexylamines; Dinoprost; Dinoprostone; Female; Humans; Immunoassay; Male; Middle Aged; Nasopharyngeal Neoplasms; Prostaglandins E

There is evidence suggesting a role of eicosanoids in the growth of certain tumors. In this study, tissue samples were collected from basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin. Both BCCs and SCCs contained more prostaglandin E2 and F2 alpha (PGE2 and PGF2 alpha) than normal epidermis. In vitro incubation of tumor samples with arachidonic acid also resulted in PGE2 and PGF2 alpha formation. Basal cell carcinomas exhibiting a histologically aggressive growth pattern contained higher levels of prostaglandins than those with a nonaggressive growth pattern, both in vivo and after in vitro incubation. Lipoxygenase products (12- and 15-hydroxyeicosatetraenoic acid) were present in smaller amounts than cyclo-oxygenase products (PGE2 and PGF2 alpha) in vivo. Compared with normal epidermis, SCCs and, particularly, BCCs produced smaller amounts of 12-hydroxyeicosatetraenoic acid during in vitro incubation with arachidonic acid. The levels of lipoxygenase products were not related to the tumor growth pattern. These results indicate that excessive prostaglandin levels in BCCs may be associated with an aggressive growth pattern.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonic Acids; Breast Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chromatography, High Pressure Liquid; Dinoprost; Dinoprostone; Head and Neck Neoplasms; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Mice; Prostaglandins; Prostaglandins E; Prostaglandins F; Rabbits; Radioimmunoassay; Skin Neoplasms

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bone Resorption; Carcinoma, Squamous Cell; Dinoprost; Dinoprostone; Humans; In Vitro Techniques; Interleukin-1; Mice; Odontogenic Cysts; Prostaglandins; Prostaglandins E; Prostaglandins F; Sarcoma, Ewing

This paper reports on the synthesis of prostaglandins in oral squamous epithelial carcinomas. Using radio-thin-layer chromatography, we observed the conversion of 14C-labelled arachidonic acid into the prostaglandins PGE2, PGF2 alpha, PGI2 and PGD2. We also observed an approximately equal production of hydroxy fatty acids. The role of the above-mentioned substances in the growth of malignant tumours and the process of metastasis is discussed.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Chromatography, Thin Layer; Dinoprost; Dinoprostone; Epoprostenol; Fatty Acids; Female; Gingival Neoplasms; Humans; Lipoxygenase; Male; Middle Aged; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Tongue Neoplasms

Topics: Animals; Bone Resorption; Calcium; Carcinoma, Squamous Cell; Culture Techniques; Dinoprost; Dinoprostone; Female; Humans; Indomethacin; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Osteolysis; Prostaglandins E; Prostaglandins F; Tongue Neoplasms; Transplantation, Heterologous

Patterns and mechanisms of local bone invasion by squamous carcinomas of the head and neck have been investigated. Detailed surgical pathology has shown that these tumors invade contiguous skeletal or metaplastic bone principally through an indirect process; the normal bone resorbing cells of the host (osteoclasts) are activated and erode bone in front of the advancing tumor edge. Tumor cells take over the destructive process when the osteoclast response has waned. These morphologic patterns have been reproduced in an in vitro model where calcium-45-labelled mouse calvaria, cocultured with a tumor for 3 days, are resorbed by osteoclasts. Freshly excised tumors, established tumor cell lines, and tumor xenografts release osteolysins in vitro which act as osteoclastic stimulants. They include both prostaglandins E2 and F2 alpha, and nonprostaglandin factors, and are derived from tumor cells and from the associated host stroma. Virtually all the tumors examined released osteolysins and resorbed bone in vitro independent of their site, size, degree of differentiation, and the presence or absence of clinical bone invasion.

Topics: Bone Neoplasms; Calcium; Carcinoma, Squamous Cell; Cell Line; Cells, Cultured; Dinoprost; Dinoprostone; Head and Neck Neoplasms; Humans; In Vitro Techniques; Laryngeal Neoplasms; Osteolysis; Prostaglandins E; Prostaglandins F

Mechanisms of bone invasion by squamous carcinomas of the head and neck have been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E2 prostaglandins (PGE2) in amounts sufficient to account for approximately 50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of the head and neck are osteolytic in vitro and release a mixture of prostaglandin and non-prostaglandin factors which stimulate osteoclastic bone resorption. These factors are derived from both neoplastic and stromal elements, and are "tumour-associated" rather than "tumour-specific". In vitro bone resorption and prostaglandin release does not correlate with pathological features of the tumour or with post-operative survival.

Topics: Animals; Bone Resorption; Carcinoma, Squamous Cell; Cell Line; Culture Media; Culture Techniques; Dinoprost; Dinoprostone; Fibroblasts; Head and Neck Neoplasms; Humans; Indomethacin; Mice; Mice, Inbred BALB C; Prostaglandins E; Prostaglandins F; Skin