Heparan sulfate proteoglycan expression in human lung‐cancer cells

• Published in: International journal of cancer Vol. 74; no. 3; pp. 335 - 345
• Main Authors: Nackaerts, Kris, Verbeken, Erik, Deneffe, Georges, Vanderschueren, Bernadette, Demedts, Maurits, David, Guido
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 20.06.1997; Wiley-Liss
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Heparan Sulfate Proteoglycans; Heparitin Sulfate - metabolism; Humans; Hyaluronan Receptors - metabolism; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphatic Metastasis; Mediastinum; Medical sciences; Neoplasm Proteins - metabolism; Pneumology; Proteoglycans - metabolism; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum; Adenocarcinoma; Human; Immunohistochemistry; Proteoglycan; Lung disease; Squamous cell carcinoma; Respiratory disease; Pathogenesis; Exploration; Malignant tumor; Carcinogenesis; In vitro; Cell surface; Bronchopulmonary; Pathology; In vivo; Histopathology; Established cell line; Bronchus disease; Heparitin sulfate
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970620)74:3<335::AID-IJC18>3.0.CO;2-A

Heparan sulfate (HS) functions as a co‐factor in several signal‐transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung‐cancer tissues and assayed for the presence of HSPGs in extracts of human lung‐cancer cell lines, using a panel of native HS‐, Δ‐HS‐ and HSPG (syndecan, glypican, CD44 and perlecan) core protein–specific monoclonal antibodies. Compared to normal epithelia, non‐small‐cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface–associated HSPGs (most consistently of syndecan‐1). CD44 or CD44‐variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix‐associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous‐cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for Δ‐HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and Δ‐HS reactions. Marked differences in HSPG expression also were observed among various non‐small‐cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype. Int. J. Cancer 74:335–345, 1997. © 1997 Wiley‐Liss, Inc.