Human-specific c-neu proto-oncogene protein overexpression in human malignant astrocytomas before and after xenografting

Abstract

Overexpression of human-specific c-neu proto-oncogene transmembrane tyrosine kinase receptor protein (p185) is an index of cell transformation and of poor patient survival in several malignancies. The authors studied this protein in low- and high-grade human malignant astrocytomas before and after xenografting into aspiration pockets in rat cortex. Human-specific p185c-neu-positive cells were found in tumor specimens from all grades of astrocytoma. Significantly fewer p185c-neu-positive cells were observed in the low-grade versus the high-grade astrocytomas examined (p < 0.05). Human specific p185c-neu-positive cells were also positive for the human major histocompatibility complex, human leukocyte antigen (HLA)-DR, as well as glial fibrillary acidic protein and S-100 protein. Fresh suspensions of tumor tissue were prelabeled with the plant lectin Phaseolus vulgaris leukoagglutinin and xenografted into pockets in rat cortex. A class of human p185c-neu-positive cells found in tissue samples from all grades of astrocytoma migrated in the rat brain along parallel and intersecting nerve fibre bundles and basement membrane-lined surfaces. Migrated p185c-neu-positive cells were also positive for HLA-DR, Phaseolus vulgaris leukoagglutinin, glial fibrillary acidic protein, and S-100 protein, suggesting that they were in fact human astrocytoma cells. Simultaneous expression of human p185c-neu, HLA-DR, and glial fibrillary acidic protein was observed in a class of human malignant astrocytoma cells in both tumor tissue and xenografted cells that migrated into rat brain. These molecules are signature proteins for the study of the spread of human malignant astrocytomas in an animal model, and indicate that transformed human malignant astrocytoma cells can migrate within the parenchyma of the central nervous system and could play a role in the development of multifocal tumors.

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

“…HER2/neu overexpression has been reported in an overwhelming majority of meningiomas despite their well-differentiated state, low-grade growth characteristics and very low metastatic potential [246][247][248][249][250]. By contrast, HER2/neu expression or overexpression has been reported as nonexistent, as with the normal embryologic expression pattern, and in some reports in up to 50% of gliomas across the range from low-grade astrocytomas to glioblastoma multiforme [247,[251][252][253][254][255][256][257][258][259][260][261] and a few activating mutations have been documented [262]. Interestingly, the special case of medulloblastoma, a subset of childhood nervous system tumors, has been documented to have a high proportion of overexpression of HER2/neu, with >30% of childhood medulloblastomas overexpressing HER2/neu [263,264].…”

Identification of renal-cell-carcinoma-related cDNA clones by suppression subtractive hybridization

“…Nonetheless, it should be pointed out that 5 of these 7 cDNA clones have been implicated in tumorigenesis. Overexpression of proto-oncogene tyrosine protein kinases (clone 5b) is considered an index of cell transformation and frequently is indicative of poor prognosis in cancer patients (Bernstein et al 1993). Several members of the ets oncogene family of transcription factors (clone 14) have been described to up-regulate promotor activities of matrix metalloproteinases, their overexpression correlating with the malignant potential of cancer cells (Hida et al 1997;Taguchi et al 1997).…”

ROS receptor tyrosine kinase: a new potential target for anticancer drugs

“…[37][38][39][40] Other RTKs include Neu, [41][42][43][44] platelet-derived growth factor (PDGF) receptor, [45][46][47][48] and ROS. In particular, the epidermal growth factor receptor (EGFR) and its associated oncogene Erb-B are noteworthy, because 45-50% malignant gliomas show evidence for EGFR amplification.…”