Vasculogenic mimicry of HT1080 tumour cells in vivo: critical role of HIF-1α-neuropilin-1 axis.

HT1080 - a human fibrosarcoma-derived cell line - forms aggressive angiogenic tumours in immuno-compromised mice. In spite of its extensive use as a model of tumour angiogenesis, the molecular event(s) initiating the angiogenic program in these cells are not known. Since hypoxia stimulates tumour angiogenesis, we examined the hypoxia-induced events evoked in these cells. In contrast to cells grown under normoxic conditions, hypoxia-primed (1% O(2)) HT1080 cells formed robust tubules on growth factor-reduced matrigel and formed significantly larger tumours in xenograft models in a chetomin-sensitive manner, indicating the role of HIF-1α-mediated transcription in these processes. Immuno-histochemical analyses of tumours formed by GFP-expressing HT1080 cells clearly showed that the tumour cells themselves expressed various angiogenic markers including Neuropilin-1 (NRP-1) and formed functional vessels containing red blood cells, thereby unambiguously demonstrating the vasculogenic mimicry of HT1080 cells in vivo. Experiments performed with the HT1080 cells stably transfected with plasmid constructs expressing shNRP-1 or full-length NRP-1 clearly established that the HIF1α-mediated up-regulation of NRP-1 played a deterministic role in the process. Hypoxia-exposure resulted in an up-regulation of c-Myc and OCT3/4 and a down-regulation of KLF4 mRNAs, suggesting their involvement in the tumour formation and angiogenesis. However, silencing of NRP-1 alone, though not affecting proliferation in culture, was sufficient to abrogate the tumour formation completely; clearly establishing that the hypoxia-mediated HIF-1α-dependent up-regulation of NRP-1 is a critical molecular event involved in the vasculogenic mimicry and tumor formation by HT1080 cells in vivo.

Solitary fibrous tumour of the face: a rare case report.

Solitary fibrous tumour is an uncommon neoplasm that arises predominantly from within the pleura. Extrapleural manifestation of solitary fibrous tumour, particularly in the head and neck area, is extremely rare. Here, we report a solitary fibrous tumour of the face in a 40-year old woman. The tumour was removed with a radiological combined approach, with embolisation of tumour blood vessels prior to excision. Eight months following surgery, the patient is well and free of disease.

Application of ligating loops to control bleeding during endoscopic surgery for a highly vascular hypopharyngeal tumour.

Endoscopic treatment of hypervascular lesions of the hypopharynx is challenging because of difficulty in controlling bleeding during surgery. We report a highly vascular hypopharyngeal solitary fibrous tumour treated by endoscopic laser surgery combined with ligating loops. Application of dual ligating loops provided easy and secure haemostasis of the feeding artery before resection. Since the endoscopic approach is less invasive than the external approach, we confirm that it is worthwhile to attempt an endoscopic approach using ligating loops before resorting to the external approach in the treatment of hypervascular hypopharyngeal lesions.

Microvessel density and HIF-1alpha expression correlate with malignant potential in fibrohistiocytic tumors.

Angiogenesis is a central process in the growth of solid tumors. Hypoxia-inducible factor-1alpha (HIF-1alpha) is an oxygen-dependent transcriptional activator, which plays a crucial role in tumor angiogenesis. However, involvement of HIF-1alpha has never been studied in so-called fibrohistiocytic tumors, such as dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH). We analyzed the extents of angiogenesis in relation to the expression levels of HIF-1alpha in 26 DF, 13 DFSP and 23 MFH cases. MFH showed significantly higher microvessel density (MVD) compared with DF and DFSP. Immunohistochemically, HIF-1alpha-positive cases constituted 31%, 15% and 98% of DF, DFSP and MFH, respectively, indicating significantly higher HIF-1alpha expression in MFH compared with DF and DFSP. Furthermore, MFH cases expressing high levels of HIF-1alpha showed significantly higher MVD than those with low levels of HIF-1alpha. Thus, higher levels of angiogenesis and HIF-1alpha expression are both closely associated with the malignant potential in so-called fibrohistiocytic tumors, and HIF-1alpha is possibly involved in angiogenesis in MFH.

Solitary fibrous tumor of the kidney originating from the renal capsule and fed by the renal capsular artery.

Solitary fibrous tumors (SFT) are relatively rare spindle cell neoplasms that typically arise in the pleura. Recently, extrathoracic SFT that have arisen in various anatomic sites have been recognized. The histogenesis and prognosis of SFT of the kidney are not well understood because only 11 cases have been reported. We report a case of SFT of the left kidney arising from the renal capsule. The tumor was merged with the upper pole of the left renal capsule. The angiography revealed that the renal capsule artery fed the tumor. The tumor was a well-circumscribed, solid mass attached to the renal capsule without necrosis or hemorrhage. Microscopically the bland spindle cells proliferated and were accompanied by hyalinized collagenous tissue showing patternless or hemangiopericytomatous patterns. Some glomeluri and renal tubules were entrapped by the tumor cells. There were no mitotic figures. Immunohistochemically the tumor cells were diffusely positive for CD34, CD99 and bcl-2. There was no evidence of recurrence after a 4 year follow-up visit. The origin of SFT of the kidney remains uncertain. The tumor in this case merged with the renal capsule and was fed by the renal capsular artery, which suggests that some SFT of the kidney originate from the renal capsule.

Orbital malignant fibrous histiocytoma with extension to the base of the skull--case report.

An 18-year-old woman presented with a malignant fibrous histiocytoma (MFH) originating in the orbit and invading the frontal and temporal base of the skull manifesting as exophthalmos and double vision that had persisted for 2 months. Magnetic resonance imaging revealed a tumor in the left orbit that extended as far as the frontal and temporal base of the skull. The tumor was treated by radical resection with conservation of the eyeball and its contents, followed by orbit wall reconstruction. The histological diagnosis was MFH. Local radiotherapy was administered postoperatively. The preoperative symptoms improved, and there has been no evidence of local recurrence or metastasis in the year since the surgery. In this case, radical resection of the tumor was essential. Furthermore, the adjuvant therapy was apparently successful, probably because this histological type of tumor is highly sensitive to radiotherapy.

Preoperative embolization of a massive solitary fibrous tumor of the pleura.

We report the case of a 69-year-old woman with a massive fibrous tumor of the left hemithorax. Initial attempted removal by median sternotomy was abandoned due to the extremely vascular appearance of the tumor and the inability to gain safe control of the pedicle. Subsequent percutaneous embolization before removal through a left thoracotomy was successful, with little intraoperative blood loss. We recommend preoperative angiography for massive chest tumors that may be vascular and require piecemeal removal for total excision.