Sphingolipids have been proposed to modulate cell function by acting as intracellular second messengers and through binding to plasma membrane receptors. Exposure of MC3T3-E1 osteoblastic cells to sphingosine (SPH), sphingosine-1-phosphate (SPP), or sphingosylphosphorylcholine (SPC) led to the release of Ca2+ from the endoplasmic reticulum (ER) and acute elevations in cytosolic-free Ca2+ ([Ca2+]i). Desensitization studies suggest that SPP and SPC bind plasma membrane endothelial differentiation gene (Edg) receptors for lysophosphatidic acid (LPA). Consistent with the coupling of Edg receptors to G proteins, SPP- and SPC-induced Ca2+ signaling was inhibited by pretreatment of the cells with pertussis toxin (PTx). Of the Edg receptors known to bind SPH derivatives in other cell types, MC3T3-E1 cells were found to express transcripts encoding Edg-1 and Edg-5 but not Edg-3, Edg-6, or Edg-8. In contrast to SPP and SPC, the ability of SPH to elicit [Ca2+]i elevations was affected neither by prior exposure of cells to LPA nor by PTx treatment. However, LPA-induced Ca2+ signaling was blocked in MC3T3-E1 cells previously exposed to SPH. Elevations in [Ca2+]i were not evoked by SPP or SPC in cells treated with 2-aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-trisphosphate (IP3)-gated Ca2+ channels in the ER. No effect of 2-APB was observed on SPH-or LPA-induced [Ca2+]i elevations. The data support a model in which SPP and SPC bind Edg-1 and/or Edg-5 receptors in osteoblasts leading to the release of Ca2+ from the ER through IP3-gated channels.
Case summaryA 15-year-old domestic shorthair cat presented for lethargy, vomiting and anorexia. Abdominal ultrasound showed a bi-lobed cystic duodenal mass. Based on ultrasonographic features, malignant transformation of a duodenal duplication cyst was suspected. A resection and anastomosis was performed. Histology of the mass was consistent with carcinoma and an intestinal mucosa was present along the inner surface of the mass, suggestive of a duplication cyst. The patient returned 3 months postsurgery with recurrence of clinical signs. Abdominal ultrasound showed a recurrent duodenal mass at the surgery site and body wall nodules. Fine-needle aspirates of these lesions showed epithelial neoplasia. Owing to the poor prognosis, the owners elected euthanasia.Relevance and novel informationMalignant transformation of duplication cysts in cats is rare but can be detected on ultrasound. The described ultrasonographic features can aid in prioritization of malignant transformation of duplication cysts as a differential diagnosis.
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