KAI-1 expression in pediatric high-grade osteosarcoma
Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9063, USA.Pediatric and Developmental Pathology (Impact Factor: 0.87). 05/2006; 9(3):219-24. DOI: 10.2350/11-05-0137.1
Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n=30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.
Article: Tetraspanins and Cancer Metastasis[Show abstract] [Hide abstract]
ABSTRACT: Metastasis formation is the final result of a cascade of events that primary tumor cells pass through by changing their phenotype and the crosstalk with the tumor environment. Molecules involved in this process are besides others tetraspanins, which surprisingly can either inhibit or promote metastasis formation. These opposing activities are supposed to rely on the special feature of tetraspanins that mostly act via modulating the activity of a multitude of associating molecules. Tetraspanins assemble a web between themselves and other associating molecules in special glycolipid-enriched membrane microdomains, which function as signaling platform, but are also prone for internalization. Internalization of tetraspanins and associated molecules by itself can contribute to promotion or inhibition of tumor progression. Notably, the internalized tetraspanin web is abundantly recovered in exosomes, small vesicles that derive from internalized membrane microdomains. Thus, it appears reasonable to assume that exosomal tetraspanins are of major importance for the crosstalk between the metastasizing tumor cell, the tumor stroma, the vessel endothelium, and the premetastatic organ. I will briefly introduce the structure of tetraspanins and their presently known main functional activities as a starting point to appreciate the contribution of selective tetraspanins in metastasis promotion and inhibition.
- Academic Journal of Second Military Medical University 09/2008; 28(2):189-192. DOI:10.3724/SP.J.1008.2008.00189
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ABSTRACT: CD82, also known as KAI-1, structurally belongs to tetraspanin family while categorised as metastasis suppressor gene on functional grounds. KAI1/CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signalling. In recent years apart from its significant involvement in the suppression of secondary tumours it has also been observed that KAI1/CD82 plays a vital role in virus binding and its entry inside the cell. Decreased expression of KAI1/CD82 molecule results in aggravating cancer progression. Altered expression levels of KAI1/CD82 molecule in different types of human cancer have been implicated as having prognostic value and linking to the long term survival of the patients. Increased level of KAI1/CD82 also results in the suppression of secondary tumour growth. Increased expression of this molecule results in reduced cell invasion and cell migration due to endocytosis of epidermal growth factor receptors (EGFR). Thus, KAI-1/CD82 is a pivotal molecule in the regulation of cancer cells' behaviour and has important clinical and therapeutic implications in cancer.Histology and histopathology 05/2009; 24(4):519-30. · 2.10 Impact Factor
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