TRPC1 channels regulate directionality of migrating cells.

Cell migration depends on the generation of structural asymmetry and on different steps: protrusion and adhesion at the front and traction and detachment at the rear part of the cell. The activity of Ca(2+) channels coordinate these steps by arranging intracellular Ca(2+) signals along the axis of movement. Here, we investigated the role of the putative mechanosensitive canonical transient receptor potential channel 1 (TRPC1) in cell migration. We analyzed its function in transformed renal epithelial (Madin-Darby canine kidney-focus) cells with variation of TRPC1 expression. As shown by time lapse video microscopy, TRPC1 knockdown cells have partially lost their polarity and the ability to persistently migrate into a given direction. This failure is linked to the suppression of a local Ca(2+) gradient at the front of migrating TRPC1 knockdown cells, whereas TRPC1 overexpression leads to steeper Ca(2+) gradients. We propose that the Ca(2+) signaling events regulated by TRPC1 within the lamellipodium determine polarity and directed cell migration.

[Hemorrhagic nonspecific pericardial effusion as an initial symptom of angiosarcoma of the right heart]. / Hämorrhagisch unspezifischer Perikarderguss als Vorbote eines Hämangiosarkoms des rechten Herzens.

HISTORY: A 45-year old woman presented at our hospital with intermittent fever in the last three weeks and progressive exertional dyspnea. In addition she suffered from physical asthenia. Seven months ago the patient was treated for symptomatic pericardial effusion in our clinic. INVESTIGATIONS: Physical examination revealed a pale skin color, epigastric pain on palpation and intense exertional dyspnea. Laboratory tests indicated microcytic anemia and high levels of LDH and CRP. The diagnosis of a large tumor of the right atrium and ventricle was based on the transthoracic echocardiogram and thoracic CT scan. The extent of the right atrial and ventricular mass of 9 x 8 cm was detected by trans-esophageal echocardiography. The thoracic and abdominal CT scan showed multiple nodular infiltrates in the basal lung fields and a cystic tumorous mass in the liver. DIAGNOSIS: The tumor developed in the short time of 7 months. Half a year ago, the transthoracic echocardiographic exam showed pericardial effusion with normal cardiac size, normal left ventricular function and no evidence of right ventricular outflow obstruction. No cardiac masses were observed. At that time pericardiocentesis was performed, but the pericardial fluid was cytologically negative for tumor cells. The diagnosis of angiosarcoma was made after surgical excision of the tumor and histological examination. There was only the possibility of a palliative therapy, because of the existence of pulmonary and liver metastases. CONCLUSIONS: Primary malignant cardiac tumors are rare and their prognosis is very poor. The heart angiosarcoma is often disseminated into the lungs and the liver at the time of clinical presentation. This case indicates that hemorrhagic nonspecific pericardial effusion, negative for tumor cells, can appear any time before a heart angiosarcoma is detectable by echocardiography.