Mesothelioma Cell Lines Using Indirect Immunofluorescence and Northern Blotting

One interesting study is called, "HLA antigen expression and malignant mesothelioma." By Christmas TI, Manning LS, Davis MR, Robinson BW, Garlepp MJ. - Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.  Am J Respir Cell Mol Biol. 1991 Sep;5(3):213-20.  Here is an excerpt: "Abstract - The expression of HLA antigens by a tumor may determine its progression and metastatic potential by influencing the immune response to that tumor. The upregulation of HLA antigen expression on some cell types by interferons (IFNs) may contribute to their antitumor activity. Malignant mesothelioma (MM) is a tumor that has a poor prognosis and is unaffected by conventional therapy, although immunotherapy has not been adequately assessed. In this study, we have examined the constitutive and IFN-inducible expression of class I and class II HLA antigens on MM cell lines using indirect immunofluorescence and Northern blotting. All MM cell lines constitutively expressed class I, but not class II, surface antigen, and all three class I loci (HLA-A, HLA-B, and HLA-C) were expressed. The MM cell lines were heterogeneous in their response to the IFNs. Treatment with IFN-alpha marginally increased class I surface expression, but not class II. Class I mRNA was, however, clearly increased in all cell lines after IFN-alpha treatment, suggesting that class I surface antigen was already maximally expressed. IFN-gamma increased class I mRNA expression in all but one cell line and induced DR expression on three of the cell lines. DQ-beta, but not DQ-alpha, mRNA was inducible in the same three cell lines, but DQ surface antigen was never demonstrable."

Another interesting study is called, "Malignant pleural mesothelioma: a problematic review" by Thomas L. Moskal, John D. Urschel, Timothy M. Anderson, Joseph G. Antkowiak, Hiroshi Takita - Volume 7, Issue 1, Pages 5-12 (July 1998).  Here is an excerpt: "Abstract - Malignant pleural mesothelioma is a rare tumor that has been difficult to study. Because of disappointing treatment results, malignant pleural mesothelioma has remained an area of active research and development. A clinicopathologic review is performed in light of several problematic issues involving diagnosis, staging, natural history, and treatment. Multimodality treatment with surgery followed by adjuvant local and systemic therapy remains the most optimal therapy. Many controversial issues still exist in the treatment of malignant pleural mesothelioma. In the ensuing years newer staging systems, better preoperative staging, newer experimental therapies, and the localization of patients at expert centers will undoubtedly have an impact on disease management."

Another interesting study is called, "Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural Mesothelioma" by V H Gerbaudo, S Britz-Cunningham, D J Sugarbaker, S T Treves - Thorax 2003;58:1077-1082 doi:10.1136 - Lung cancer.  Here is an excerpt: "Abstract - Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable course. This pilot study evaluated the significance of the pattern, intensity and kinetics of 18F-FDG uptake in mesothelioma in the context of histopathology and surgical staging.

Methods: Sixteen consecutive patients with pleural disease on CT scan underwent 18F-FDG imaging. Imaging was performed with a dual detector gamma camera operating in coincidence mode. Semiquantitative image analysis was performed by obtaining lesion-to-background ratios (18F-FDG uptake index) and calculating the increment of 18F-FDG lesion uptake over time (malignant metabolic potential index (MMPi)).

Results: Twelve patients had histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid). Thirty two lesions were positive for tumour. Patterns of uptake matched the extent of pleural and parenchymal involvement observed on CT scanning and surgery. Mean (SD) 18F-FDG uptake index for malignant lesions was 3.99 (1.92), range 1.5–9.46. Extrathoracic spread and metastases had higher 18F-FDG uptake indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No correlation was found between histological grade and stage. The intensity of lesion uptake had poor correlation with histological grade but good correlation with surgical stage. 18F-FDG lesion uptake increased over time at a higher rate in patients with more advanced disease. The MMPi was a better predictor of disease aggressiveness than the histological grade.

Conclusions: This pilot study suggests that the pattern, intensity, and kinetics of 18F-FDG uptake in mesothelioma are good indicators of tumour aggressiveness and are superior to the histological grade in this regard."

Another interesting study is called, "Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction." By Klominek J, Baskin B, Hauzenberger D. -
Clin Exp Metastasis. 1998 Aug;16(6):529-39.  Here is an excerpt: "Abstract - Platelet-derived growth factor BB (PDGF BB) and the PDGF receptor beta are expressed on mesothelioma cells, but their biological function has not yet been defined. In the present study we used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV or the nonmatrix adhesive molecule poly-L-lysine (PLL). Mesothelioma cells migrated towards PDGF BB at concentrations ranging from 0.78 to 12.5 ng/ml if matrix proteins were present as adhesive substrates. This migration was integrin dependent since the same cells failed to migrate if the adhesive interactions necessary for migration were provided by molecules other than integrins. Migration of mesothelioma cells on fibronectin, laminin or collagen-type IV in response to PDGF BB was inhibited if the cells were pretreated with blocking antibodies to alpha3beta1 integrin. These findings describe for the first time PDGF BB as a chemoattractant for malignant mesothelioma cells and that collaboration between PDGF receptor beta and integrin alpha3beta1 is necessary for the motile response of these cells to PDGF BB."

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.