KAI-1 expression in pediatric high-grade osteosarcoma.
ABSTRACT 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: Aims and background. Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. Methods. We investigated the expression of two metastasis-suppression genes - KAI-1 and KiSS-1 - and a metastasis-associated gene - MTA1 - in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. Results. We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. Conclusions. Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.Tumori 11/2014; 100(6):667-74. DOI:10.1700/1778.19276 · 1.09 Impact Factor