Expression of hyaluronan in normal and dysplastic bronchial epithelium and in squamous cell carcinoma of the lung.
ABSTRACT A series of 85 lung/bronchial tissue samples from 76 patients consisting of normal, metaplastic and dysplastic epithelium and different types of lung carcinomas were analyzed for the distribution of hyaluronan (HA), using a biotinylated hyaluronan binding complex as an HA-specific probe. The normal pseudo-stratified columnar bronchial epithelium was either negative for HA or displayed a weak staining around the basal cells. The epithelia of serous and mucous bronchial glands were HA negative whereas the submucosal connective tissue was strongly positive. In metaplastic, dysplastic and carcinoma in situ lesions the whole epithelium from basal to uppermost cells expressed HA on plasma membranes. Epithelial HA was also found in squamous cell carcinomas, but not in adenocarcinomas, carcinoid tumors or small cell carcinomas of the lung. Whereas epithelial HA was present in all lesions of the squamous cell type, the staining intensity displayed great local variability in 50% of the cases with severe dysplasia, carcinoma in situ and squamous cell carcinomas. In squamous cell carcinomas, such an irregular staining pattern was significantly associated with poor differentiation. Our results indicate that the expression of HA in different bronchial lesions and lung tumors is restricted to those showing squamous cell differentiation, being absent from other types of lung carcinomas. The increase of HA depleted areas in poorly differentiated squamous cell carcinomas emphasizes the important role of HA in tumor differentiation. HA on carcinoma cell surface may influence tumor growth and metastatic behavior.
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ABSTRACT: In the present study, we examined the metastatic potential of tumor cells expressing different levels of cell surface hyaluronan. We used flow cytometry to isolate subsets of the B16-F1 mouse melanoma cell line that expressed either high (HA-H) or low (HA-L) amounts of hyaluronan on their surfaces. These two subsets of cells showed a 32-fold difference in the amount of cell surface hyaluronan, due to its rate of synthesis. However, these cell lines did not differ from each other with regard to their in vitro growth rates, susceptibility to natural killer-mediated cytotoxicity, or the expression of the cell surface proteins CD44, ICAM-1, and GMP-140. When these cells were injected s.c., they both formed s.c. tumors of approximately the same size. However, when injected into the tail vein of mice, the HA-H cells formed a greater number of nodules in the lungs and caused a faster rate of mortality than the HA-L cells. The presence of hyaluronan did enhance the interaction of the HA-H cells with cultured endothelial cells that expressed CD44. Thus, it is possible that enhanced interactions between hyaluronan and CD44 promoted the formation of tumor embolisms which, in turn, increased the chances that the tumor cells would be trapped in the lungs. Taken together, these results suggest that hyaluronan may play a critical role in the process of tumor metastasis.Cancer Research 02/1995; 55(2):428-33. · 8.65 Impact Factor
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ABSTRACT: Lung cancer continues to be a leading cause of preventable death, with an estimated 123,000 of the 143,000 lung cancer deaths in the United States in 1991 directly attributable to tobacco smoking. Given that mortality from this disease has not changed appreciably in the past two decades and despite continuing advances in cancer treatment, a new emphasis is being placed on prevention and early detection research through the identification of high-risk individuals and the definition of useful biomarkers. This review summarizes the status of these efforts over the past year.Current Opinion in Oncology 04/1993; 5(2):302-9. · 4.03 Impact Factor
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ABSTRACT: Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.The Journal of Pathology 01/1996; 177(4):363-8. · 7.59 Impact Factor