Suppressive Effects Of Mesothelioma Tumors
An interesting study is called, Dickkopf-1 antagonizes Wnt signaling independent
of -catenin in human Mesothelioma - Biochemical and Biophysical Research Communications - Volume 323, Issue 4, 29 October 2004, Pages 1246-1250 by Amie Y. Lee, Biao He, Liang You, Zhidong Xu, Julien Mazieres, Noemi Reguart, Iwao Mikami, Sonny Batra and David M. Jablons Here is an excerpt: Abstract - Dickkopf-1 (Dkk-1) is a secreted protein that acts as a potent inhibitor of the Wnt signal transduction pathway. It is thought that the antagonistic effect of Dkk-1 is specific to the canonical (Wnt/-catenin) pathway. In this study, we demonstrate that restoration of Dkk-1 expression suppresses cell growth and induces apoptotic cell death in -catenin-deficient mesothelioma cell lines H28 and MS-1. Furthermore, we found that a small-molecule inhibitor of JNK inhibited the apoptosis induced by Dkk-1 overexpression in these cells. Together, our data suggest that Dkk-1 may be able to antagonize Wnt signaling and exert its tumor suppressive effects through -catenin-independent non-canonical pathways.
Another interesting study is called, Lysis of human malignant mesothelioma cells by natural killer (NK) and lymphokine-activated killer (LAK) cells. By Manning LS, Bowman RV, Darby SB, Robinson BW. - Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia. Am Rev Respir Dis. 1989 Jun;139(6):1369-74. Here is an excerpt: Abstract - Malignant mesothelioma is an aggressive tumor of the pleura for which, at present, there is no effective therapy. As interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells lyse many solid tissue malignancies that are unresponsive to conventional forms of therapy, the aim of this study was to evaluate the susceptibility of human malignant mesothelioma cells to lysis by natural killer (NK) and LAK cells. Using a 4-h 51Cr release assay, malignant mesothelioma cell lines grown from six different patients were found to be resistant to NK cell lysis (less than 10% lysis as compared to 50 +/- 3% lysis of the standard NK-sensitive target, K562, p less than 0.001). These malignant mesothelioma cells were, however, susceptible to lysis by LAK cells (58 +/- 4% lysis, p less than 0.001 compared to NK lysis). Similar results were seen using fresh mesothelioma cell targets (4 +/- 2% and 34 +/- 12% lysis for NK and LAK cells, respectively). Optimal LAK cell activation against these targets was achieved by incubating peripheral blood mononuclear cells (2 to 4 x 10(6)/ml) in culture medium containing 1,000 units/ml IL-2 for 3 to 14 days. The degree of LAK cell activation was dependent on the serum source used in culture, with autologous serum being more effective than pooled human AB serum or fetal calf serum at generating LAK cell activity in vitro (p less than 0.05). The results of this study demonstrate that although human malignant mesothelioma cells are resistant to NK cell lysis, IL-2-activated LAK cells effectively kill these targets.
Another interesting study is called, Differentiation of Mesothelioma Cells Is Influenced by the Expression of Proteoglycans - Experimental Cell Research - Volume 258, Issue 1, 10 July 2000, Pages 12-22 by Katalin Dobraa, Michael Andngb, Alexandra Syrokouc, Nikos K. Karamanosc and Anders Hjerpea Here is an excerpt: Abstract - Malignant mesothelioma characteristically shows epithelial and/or sarcomatous morphology, this phenotypic differentiation being correlated to the prognosis. The present study was undertaken to see whether proteoglycan (PG) expression influences mesothelioma differentiation. To assess this hypothesis, we studied a mesothelioma model, where the cells were induced to differentiate into epithelial or fibroblast-like morphology, mimicking the biphasic growth of this sarcoma. Series of PGs were analyzed in parallel by semiquantitative reversed transcriptase polymerase chain reaction, showing increased expression of syndecan-2, syndecan-4, and hyaluronan synthase in the epithelial phenotype, whereas the fibroblast-like cells expressed more matrix PGs: versican, decorin, and biglycan. Western blotting confirms these differences and provides evidence of extensive shedding and rapid turnover of cell membrane PGs. Experimental down-regulation of the studied syndecans by antisense targeting resulted in a change in shape from polygonal to spindle-like morphology, while syndecan-1 and -4, but not syndecan-2, could be associated with cell aggregation, indicating distinct functions of different syndecans. The PG profile is thus closely associated with the morphology and biological behavior of tumor cells, mesotheliomas showing a different profile than true epithelial tumors.
We all owe a debt of gratitude to these fine researchers for their work. If you found any of these excerpts helpful, please read the studies in their entirety.
by: Mont Wrobleski
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