Coexpression of HGF and c‐Met/HGF receptor in human bone and soft tissue tumors

Abstract

To understand the interaction between hepatocyte growth factor (HGF) and its receptor c-Met on various bone and soft tissue tumors, their expressions were investigated by western blot analysis, immunohistochemistry and enzyme immunoassay. Western blot analysis revealed that c-Met protein was expressed in 21 (38.8%) of 54 tumors, which detailed to seven (25.9%) of 27 bone tumors and 14 (51.8%) of 27 soft tissue tumors. Most malignant fibrous histiocytomas (MFH) and all neurofibromas expressed c-Met protein. The highest expression of c-Met protein was seen in a case of biphasic synovial sarcoma, where its immunoreactivity was localized only on the epithelial component and not on the sarcomatous component. By enzyme immunoassay for HGF, all but one MFH showed HGF production and the mean level of HGF was the highest among the tumors investigated. Neurofibromas and osteosarcomas had the next highest mean levels of HGF production, respectively. Coexpression of HGF and c-Met was observed in 19 (35.2%) of 54 tumors and was frequently observed in neurofibroma, followed by MFH and synovial sarcoma. Although the mode of interaction between HGF and c-Met varies among the various bone and soft tissue tumors including MFH, their signaling system may play an important role in the development and progression of bone and soft tissue tumors.

Acquisition of biologically relevant gene expression data by Affymetrix microarray analysis of archival formalin-fixed paraffin-embedded tumours

“…These proteins were significantly upregulated in malignant compared to benign soft tissue tumours (implicating a role in tumorigenesis) and moreover significantly increased the risk of metastasis development in our samples. Cmet has previously been detected in 52 -87% of STS (Fukuda et al, 1998;Kuhnen et al, 2003) and, an important protooncogene itself, also enables sarcoma cells to become hyperresponsive to HGF, a ubiquitously expressed effector of cell proliferation, motility and invasiveness (Cortner et al, 1995). Dysregulation of TRKB and its activating neurotrophin BDNF play a role in tumorigenesis and metastasis in a wide range of carcinomas (Han et al, 2007) but, to our knowledge, a role for TRKB in sarcoma tumorigenesis and metastasis development has not previously been described.…”

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

“…The preferential effect on motility reflects the known expression of the tpr-met oncogene by the MNNG cell line [51,55]. Overexpression of HGF and met/ HGF-R has been demonstrated in patients with osteosarcoma [15,17] and causes malignant transformation of primary osteoblasts [52]. HGF increases motility, proliferation, and invasion of osteosarcoma cells [11,42].…”

“…Because many of the receptors and downstream signaling molecules are tyrosine kinases [18,22], inhibitors of these kinases are a majority of the most promising anticancer drugs [4,10,21,27]. Although osteosarcoma has not been as well studied as other types of cancer, overexpression in osteosarcoma has been reported for both growth factors and their tyrosine kinase receptors, and overexpression of some of these molecules correlates with metastasis and poor survival in patients with osteosarcoma [5,8,9,15,17,20,23,28,33,36,47,49,60,65].…”

Adaptor Molecule Crk Is Required for Sustained Phosphorylation of Grb2-Associated Binder 1 and Hepatocyte Growth Factor–Induced Cell Motility of Human Synovial Sarcoma Cell Lines

“…Synovial sarcoma occurs primarily in the extremities of young adults, especially in the periarticular region, and often metastasizes to the lung. Interestingly, both HGF and c-Met have been found to be overexpressed in synovial sarcoma (34)(35)(36). The autocrine mechanism of HGF is thought to be involved in tumor growth and an epithelial-mesenchymal transition in this sarcoma (37,38).…”